ISSN : 2394-4536 (Print)
esearch News
Vol. 3 No. 1 & 2 December 2014
A Half Yearly News Letter of Indian Virological Society on Research and Development in the Field of Virology
IVS President Desk
depend on which avian influenza A virus caused the infection. Low pathogenic avian influenza A virus Avian influenza A virus in Human
infections of humans have been associated with The current burden of influenza in generally mild, non fatal illness. Highly pathogenic India is serious. In India, it is estimated avian influenza A virus infections of humans have been that approx. 24,000 children under 5 associated with a wide range of illness. Illness has years of age die of Flu alone; a figure ranged from conjunctivitis only, to influenza-like illness, amounting ¼ th of total deaths in the to severe respiratory illness with multi-organ disease, world. The figures for most of the sometimes accompanied by nausea, abdominal pain, counties in South-East Asia are more or diarrhea, vomiting and sometimes neurologic changes less similar and higher. A study carried out by AIIMS, (altered mental status, seizures). Sometimes infection Delhi team on ‘Trends of circulating influenza viruses in with highly pathogenic avian influenza A virus infection a rural community under surveillance: impact on leads to death, especially with HPAI H5N1 virus. The vaccination timing' over 3 years period during 2009-12 accuracy of clinical diagnosis of human infection with suggested peaks during July to September, a strong avian influenza A viruses on the basis of signs and suggestion for influenza vaccination.
symptoms alone is limited because symptoms from Avian influenza a virus infections in humans.
illness caused by other pathogens, including seasonal Since November 2003, more than 600 sporadic cases influenza A or B viruses, can overlap considerably.
of human infection with highly pathogenic avian Detecting avian influenza a virus infection in
influenza (HPAI) A (H5N1) virus with high mortality have humans. Avian influenza A virus infection in humans
been reported, primarily by 15 countries in Asia, Africa, cannot be diagnosed by clinical signs and symptoms the Pacific, Europe and the Near East. On January 8, alone; laboratory testing is requiredto diagnose by 2014, the first case of a human infection with H5N1 in collecting a swab from the nose or throat of the sick the Americas was reported in Canada. Besides, H5N1, person during the first few days of illness. This there are few more odd numbers of avian influenza specimen is sent to a lab; the laboratory looks for avian virus has been seen to cause infection in human influenza A virus either by using a molecular test, by (H5N2, H7N9, etc.). Most human infections with avian trying to grow the virus, or both.
influenza A viruses have occurred following direct or Treating avian influenza a virus infections in
close contact with infected poultry. Illness in humans humans. CDC and WHO recommend oseltamivir or
has ranged from mild to severe. zanamivir, two of four prescription antiviral medications Because HPAI H5N1 viruses are evolving in currently licensed for use in the United States, for unpredictable ways, it is critical to monitor the spread treatment and prevention of human infection with avian and circulation of these viruses among poultry and influenza A viruses. Analyses of available HPAI H5N1 other birds, in order to understand the risk of spread to viruses circulating worldwide suggest that most viruses are susceptible to oseltamivir and zanamivir. However, Signs and symptoms of avian influenza a virus
some evidence of resistance to oseltamivir that infections in humans. Signs and symptoms may
developed has been reported in HPAI H5N1 viruses isolated from some human cases. Monitoring for In this Issue
antiviral resistance among avian influenza A viruses is crucial and ongoing to inform CDC and WHO antiviral From IVS President desk .1 International Conference .2Research News.2 Preventing human infection with avian influenza
Oral vaccine development against viral diseases in fish a viruses. The best way to prevent infection with avian
using structure-based antigen.2 influenza A viruses is to avoid sources of exposure. Establishment of epigenetic mechanism to control Most human infections with avian influenza A viruses geminivirus infection in tomato .4 have occurred following direct or close contact with DNA Chip for detection of globally known viruses and infected poultry.
viroids infecting plants .5Mechanisms and treatments for inflammation caused by A.K. Prasad
President, Indian Virological Society, The emergence of the novel promoter variant strains of HIV-1 in India and other global regions .6 (Source of Information: WHO/CDC (Atlanta)/ NCDC, AIIMS, Delhi Novel adjuvant technology for effective and stable vaccines 8 and Government of India Published Data.) www.ivsnet.in VirusResearch News3(1&2) Page 2 However, there are a very few commercially available oral INTERNATIONAL CONFERENCE
vaccines, such as the ISA oral vaccine sold by Centrovet, Chile, or via immersion such as the KHV vaccine recently The 8th International Geminivirus Symposium approved in the US and Canada. While oral vaccination is a and the 6th International ssDNA Comparative "holy grail" in aquaculture, since it offers low labor and lower Virology Workshop cost, developing such an effective vaccine is also the most The ssDNA workshop is scheduled to be held between 6 and 11 November, 2016 at New Delhi. The symposium will Structure based design methods have been employed to present an excellent platform to discuss and share the latest develop viral vaccines have been developed to provide developments in the subject of geminiviruses and ssDNA broad spectrum protection in humans. We are applying viruses of plants, animals and human beings. The sessions will similar approaches to aquaculture vaccine development. deal with topics such as Replication, Recombination, Virus- Previously we developed vaccines against viral diseases in plant interactions, Virus-vector interactions, Viral Diversity, fish (IPNV VLP vaccine, c-myc VLP) using the primary Resistance, Satellites, Emerging/Novel viruses, etc. About structure of the antigen.
one hundred delegates from all over the World are expected to IHNV G-protein structure-based vaccine development at attend the symposium. Special sessions will be organized to give promising young scientists an opportunity for oral presentation of their research. Dedicated poster sessions will be available to enable close scientific interactions to take place between the delegates. There will also be facilities for commercial organizations to showcase their products to an international audience. Concessional rates for registration will be made available for PhD students and post-doctoral fellows. More information will soon be available in IVS website. Oral vaccine development against viral
diseases in fish using structure-based

BrioBiotech. There is already a DNA vaccine was against IHNV but emergence of new IHNV strain poses a continuing threat to salmonid aquaculture because the existing vaccine F. C. Thomas Allnutt and Arun K. Dhar
may not provide adequate protection against the newly BrioBiotech LLC, P. O. Box 26, Glenelg, Maryland 21737, USA emerging strain.We generated molecular models of a Correspondence to Arun K. Dhar (E-mail: [email protected]) monomer of the glycoprotein of an IHNV strain representing genogroup E (Fig. 1). Conserved disulfide bonds in the core Diseases caused by bacteria, viruses and parasites are a of the protein are displayed as yellow spheres. Antigenic threat to sustainable growth of fisheries globally. Although regions have been identified in the literature. A model bacterial diseases are more prevalent, viral diseases surface representation of the trimer is on the right with these cause more economic loss worldwide. Infectious antigenic regions colored: aa 78-81 (red), 218-233 (yellow), hematopoietic necrosis (IHN), infection salmon anemia 272-276 (blue), and 301-325 (green). All are preditedto be (ISA), infectious pancreatic necrosis (IPN), and koi herpes surface exposed by this model. Another conserved region virus (KHV or CyHV-3) are examples of major viral (aa 419-444) is predicted to be buried. BrioBiotech is diseases that have caused catastrophic losses in finfish targeting the surface exposed regions and using aquaculture. Improving animal health through vaccination bioinformatics to identify variation in these antigenic regions is one of the corner stones in disease management in between strains of IHNV to better design a broadly aquaculture and in other organisms (including humans). applicable vaccine.
There are different types of viral vaccines including killed or attenuated live viruses, major antigen(s) expressed as Using oral delivery methods and in situ generation of recombinant protein(s), DNA vaccines and virus-like vaccines in microbial hosts used for production that can be particle-based vaccines developing a vaccine that will directly included in the delivery formulation allows provide broad protection against a number of widely development of vaccines that are able to address many prevalent strains of a particular virus remains a real variants of the virus in a single formulation.
challenge in fin fish aquaculture.
BrioBiotech is dedicated in addressing this issues that fish Irrespective of the type of vaccine used in aquaculture, the farmers and fish industry needed badly worldwide.
overwhelming delivery method is through injection. www.ivsnet.in VirusResearch News3(1&2) Page 3 Establishment of epigenetic mechanism to
this, it could be inferred that both siRNA-mediated RNA control geminivirus infection in tomato
degradation and viral DNA methylation are the two modes of epigenetic regulation, which play an important role in conferring tolerance against ToLCNDV. Our research outcomes may have significant impact not only on tomato, but also on the crops whose survival and productivity is challenged by viruses. Pranav Pankaj Sahu, Namisha Sharma and Manoj
DNA Chip for detection of globally known
viruses and viroids infecting plants
National Institute of Plant Genome Research, Aruna Asaf Ali Marg, New Delhi-110067, India Correspondence to Manoj Prasad ([email protected]) Epigenetic mechanism has emerged as a promising approach to decipher the stress tolerance in crop plants. This mechanism commences with the accumulation of small interfering RNAs (siRNAs) which in turn directs V. K. Baranwal, Saritha. R. K. and R. K. Jain
O.D. at 405 nm
transcriptional gene silencing (TGS) and post- Advanced Centre for Plant Virology, Division of Plant Pathology, IARI, New Delhi transcriptional gene silencing (PTGS; Recent studies have Correspondence to VK baranwal ([email protected]) highlighted the incidence of epigenetic regulation during virus infection in plant systems. In our lab, we have identified 1:100 1:200 1:1000 1:2000 1:4000
the existence of similar mechanism in a naturally tolerant DNA microarray is a promising new technology that allows cultivar of tomato (H-88-78-1), against Tomato leaf curl New the broad spectrum detection of plant viruses allowing Delhi virus (ToLCNDV).
parallel detection of thousands of viruses. DNA chip was designed on affymetrix platform which has probes to detect With an aim of dissecting the ToLCNDV tolerance all viruses andviroids (1155) whose sequences were Fig.1. Detection of Cucumber mosaic virus (CMV) by ELISA kit. (a) mechanism, we initially screened the available tomato Cucumber plant showing mosaic symptom following inoculation of available in the GenBank. A set of 7-11 unique probes was germplasms for identifying naturally tolerant cultivars. This CMV. (b) Distorted small fruit from the CMV infected plants. (c) CMV designed for family, genus and virus and viroid from the particle and (d) ELISA detection of CMV by using polyclonal antibodies exercise successfully identified two cultivars namely ‘H-88- sequences available in GenBank.There are 1572 probe to recombinant capsid protein of CMV 78-1' and ‘LA1777' as ToLCNDV tolerant varieties where sets totaling to 17292 unique probes for detection of viruses tolerance of both the cultivars was attributed to the &viroidson the chip. Housekeeping genes of sequenced production of higher amount of ToLCNDV-derived siRNAs plant species areincluded as controls.This unique chip is Our studies showed that diverse species (21- and 24- nucleotide) of siRNAs tend to regulate TGS and PTGS first of its kind in India to reveal plant virome. The chip can pathways in a stringent manner. While comparing the siRNA detect both DNA and RNA viruses in a single assay. Both levels in tolerant cv. ‘H-88-78-1' and susceptible cv. ‘Punjab DNA and RNA viruses can be detected using the same Chhuhara' in response to ToLCNDV infection, a higher chipstarting from as little as 25 ng of total plant RNA.cDNA accumulation of siRNAs corresponding to the Intergenic is prepared from total RNA using random primers and viral Region (IR) and region specific to replication associated protein (AC1) of ToLCNDV DNA-A genome was observed in invitrotranscription. cDNA to the tolerant cultivar. the amplified RNA is then labeled and hybridized on the Recently, siRNA-mediated DNA methylation mechanism chip. Amount of hybridization has been evidenced to be a pivotal component in epigenetic is assessed by a laser regulation of geminivirus tolerance. Therefore, the levels of DNA methylation in the region where elevated levels of inferences are made by siRNAs were identified i.e. specific to IR and AC1, were scanned. The result indicated the hyper-methylation of comparing with healthy cytosines in various regions of IR and AC1. Furthermore, samples. Several viruses and hyper-methylation in IR was assumed to regulate the viroids, from different crops expression of the genes responsible for virus replication, like chilli, grapevine, tomato, which was confirmed by the expression analysis of respective gene. More importantly, the key host sugarcane were detected. methyltransferases (such as, Domain rearranged Viruses which do not induce DNA chips developed at IARI, methyltransferase, and Chromomethylase-3) and symptoms could also be New Delhi for the detection of components of RNA silencing pathways (Dicer-like proteins3-4 and Argonaute 1) were also evidenced to be detected viruses were not differentially expressed in cv. ‘H-88-78-1' during ToLCNDV known to occur in India.This infection. Thus, establishment of DNA methylation chip will be a valuable tool to identifyexotic and emerging maintaining enzymes along with RNA silencing machinery virusesto initiate quarantine measures as wellas to prepare also accentuates the existence of DNA methylation- geographical distribution of different viruses infecting mediated tolerance in tomato against ToLCNDV. In view of different crops in the country.
www.ivsnet.in VirusResearch News3(1&2) Page 4 Mechanisms and treatments for inflammation
the Australian investigators to the discovery that drugs caused by alphaviruses
which block MIF have the potential to reduce the severity of alphavirus-induced arthritis, alleviating the suffering of millions around the world. We have also made a significant contribution to the study of antibody-dependent enhancement (ADE), a phenomenon which sees the immune system unable to fight off infection with a variant of a virus to which it has been exposed previously. My lab was the first to discover how this signalling pathway can lead to suppression of host Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia. ([email protected]) immunity by arboviruses. ADE commonly occurs with the dengue virus- a mosquito-borne virus that infects around Chikungunya is a disease without a cure, infecting millions 100 million people each year. Dengue virus can be of people around the world during the peak of an outbreak in separated into four serotypes, and previous infection with 2006, which centred around the Indian Ocean. Although it one serotype can hinder recovery from a later infection with generally has a low mortality rate, Chikungunya virus a different serotype. We found that the genes which (CHIKV) belongs to a group of viruses known as normally lead to the production of antiviral proteins are alphaviruses (familyTogaviridae) that can frequently cause
disrupted in ADE and thus key antibodies required to fight rheumatic symptoms associated with arthritis in the infected off the infection do not appear. This information not only patient. The acute symptoms of CHIKV infection often provides an explanation for a phenomenon first observed in subside after a few days or weeks but the arthritis can linger 1964, but also facilitates the production of effective on for much longer, causing chronic pain for the sufferer. vaccines against viral infections. The work received much Other such viruses include Ross River virus (RRV), the publicity, featuring as a special commentary in Trends in most common mosquito-borne infection in Australia, and Immunology, a monthly journal focusing on advances in the o'nyong'nyong virus, which infected over 2 million people in East Africa during a 1959-62 epidemic.
In the search to reduce the symptoms of arthritis, our Our team is working to find out a treatment for the team was successful in looking at new applications for pre- arthritogenic infection. The mechanism by which the existing drugs. This has made the leap from theory to arthritis is caused is not yet understood: what is known, clinical trial much quicker because the lengthy process of however, is that macrophages are of major significance in obtaining drug approval for human trials by a national this process. Our group found macrophage migration health agency has already been completed. Our basic inhibitory factor (MIF)- a protein involved in the regulation of research identified the macrophage as a crucial macrophage function to play a key role in determining the immunopathological component in viral arthritis and, based severity of arthritis caused by alphaviruses. Although, on this discovery, we sought to test drugs that can inhibit macrophages form a vital component of the immune migration of macrophages into infected joints. Our team system, they can act to exacerbate symptoms of virus- identified bindarit as one such drug, and testing in mouse induced arthritis, causing the destruction of soft tissue and models of CHIKV and RRV arthritis, revealed that bindarit increasing inflammation in the joints. This research has led had potent therapeutic activity against viral arthritis. Bindarit is a drug produced by Angelini Pharmaceuticals and is currently in clinical development for the treatment of type 2 diabetes nephropathy and for prevention of coronary in-stent restenosis. This means that the drug already has a well-established clinical safety profile and Mahalingam is currently planning clinical trials for bindarit treatment of patients infected with CHIKV.
Collaboration has proved essential in carrying out this multidisciplinary research, and much work has been done under the flag of the Forum for European-Australian Science and Technology cooperation (FEAST). We are also involved in a large collaboration including six laboratories in Australia and India (Professors Shobha Broor and Lalit Dar, AIIMS, New Delhi) which is focusing on combating CHIKV in India. We are also involved in is Integrated Chikungunya Research (ICRES), supported by the EU. Our findings and mouse models will be incorporated into the project to eventually produce a vaccine for clinical trials against CHIKV infection in humans. The team also offers their expertise in animal models of viral infection (chikungunya, dengue, respiratory viruses) and inflammation (rheumatoid arthritis, asthma) to Fig. 1. Vero cells infected with alphavirus.
third parties, particularly biotechnology companies. www.ivsnet.in VirusResearch News3(1&2) Page 5 The emergence of the novel promoter variant
the overall strength of the promoter. Could the presence of a strains of HIV-1 in India and other global
stronger viral promoter be one of the reasons underlying the global success of subtype C? When other HIV-1 subtypes contain 2 NF-kappaB sites, why should subtype C alone contain 3 such elements in its promoter? As we were striving to find a logical answer to the above question, we found something more appalling in India. The emergence and rapid expansion of novel HIV-1 strains containing 4 NF-kappa B binding sites. A decade ago, in 2000-2003, we found at least two different variant viral strains emerging in small numbers. Jawaharlal Nehru Centre for Advanced Scientific Research, One of the two types contained 4 NF-kappaB sites when the native viral strains contain only three such elements. The other type contains 2 RBEIII binding sites (like NF-kappaB, Human immunodeficiency virus 1 (HIV-1) (genus Lentivirus, RBEIII is a different and important transcription factor), family Retroviridae) there are many genetic families that are while the native viral strains contain only one RBEIII referred to as subtypes (or clades) A to K. Of the at least 9 element (Mahesh Bachu et al, AIDS Research and Human primary genetic subtypes, subtype C commands a special Retroviruses, 28, 1262-8, 2012). These new viral strains position as this family alone is responsible for nearly half of were found at a prevalence of only 1-2% at that time. A the global HIV infections. Over the past decades subtype C decade later, we received a big jolt to find that these two prevalence has been progressively on the rise from 25-48% as of today. In India, more than 95% of the infections of HIV-1 are attributed to subtype C. This subtype is also the major one in China (although as a recombinant), eastern and southern African countries and presently emerging in Infection, but
southern Brazil. no disease or
The African primates and their natural Simian immunideficiency virus (SIVs) evolved together over African green monkey
several thousands of years shaping the evolutionary trajectory of each other. As a consequence, the natural SIV Chronic infection,
is infectious, but not pathogenic for its own host. AIDS and death
Reciprocating this favor from the parasite, the natural primate host will not be hostile to own natural SIV. Although this association is not a symbiosis, where both the species Infection, but
are benefited be each other, at least they do not harm each no disease or
other. We therefore can call this association ‘a peaceful coexistence'. Of note, the SIV strain may not be pathogenic for its natural host, but the virus will destroy a different primate species if injected experimentally (Figure-1). In other words, the virus hasn't really become non-pathogenic, it only attenuated itself to tolerate its natural primate host. and SIV are viruses like HIV that infect in the wild their own natural primate hosts the African Green Monkey and the Sooty Extending this observation further, can we say that HIV-1 is Mangabee, respectively. Infection by the natural viruses does not cause likely to undergo a similar evolutionary adaptation to disease or death in the natural hosts. However, if a virus is become progressively less pathogenic to the human experimentally introduced into a wrong host, there will be disease beings? This is the real question. progression that ultimately leads to the death of the wrong host.
A school of thought proposes that subtype C of the promoter variant strains grew to 20-35% in India (Mahesh diverse subtypes of HIV-1 has taken a step in the direction of Bachu et al, Journal of Biological Chemistry, 287, 44714- making itself less pathogenic to the human beings. Could 35, 2012). The new viruses have been expanding at a rapid this be one reason for the successful global expansion of pace replacing the native viral strains. The emergence of subtype C over the years? The work emerging from our the new promoter-variant viral strains is not unique to India, laboratory in the recent years supports this proposition. but can be seen in other countries where subtype C is Most of the viral proteins, such as Tat and envelope of prevalent such as South Africa and China. A recent subtype C appear to be toned down versions of toxicity as publication from Brazil too confirmed the emergence of the compared to their counterparts from other viral subtypes. variant viral strains in that country (Boullosa J, et al, The viral promoter alone appears to be superior in subtype Viruses, 6, 2495-2504, 2014). C as compared to other subtypes. While the promoter in Using a wide range of molecular strategies, we proved subtype C alone contains 3 NF-kappaB binding motifs, in that the novel viral strains containing 4 NF-kappaB sites most of the other viral subtypes there are only 2 such motifs. (the 4-kB strains) in the promoter dominate the genetically The number of the NF-kappaB sites typically correlates to www.ivsnet.in VirusResearch News3(1&2) Page 6 similar viral strains that have only 3 such motifs (the 3-kB Novel adjuvant technology for effective and
strains). Importantly, the 4-kB strains make more daughter viruses from the target cells as compared to the 3-kB strains. Additionally, people infected with the 4-kB strains contained more number of viral particles in their blood than those infected with the 3-kB strains. We generated substantial experimental evidence and proved that only subtype C, but not other HIV-1 subtypes, has a potential to acquire the additional NF-kappaB motif. Don't forget that Prem Sagar , Ben Arous J , Bertrand F and Sebastien
subtype C played this trick once before to acquire a third NF-kappaB site. Subtype C repeats that trick once again to 1 SEPPIC, O2, Commercial Twin Tower, B/1304, Asha Nagar Road, acquire a fourth NF-kappaB site. We presently have some Malad West, Mumbai-400 080 experimental evidence to explain how subtype C plays this 2 SEPPIC, 22 Terrase Bellini, Paris La Defense, 92806 PuteauxCedex, France trick at the molecular level. Correspondence to Prem Sagar ([email protected]) Our findings raise many important questions. A stronger viral promoter may positively contribute to the successful Adjuvants are compounds that enhance the specific expansion of the variant viral strains. This proposition, immune response against co-inoculated antigens. The role however, appears to be counterintuitive because the of adjuvants was noticed in 1920s from observations of consequential stronger viral gene expression should also Ramon et al. who noted that horses that developed an elicit a stronger immune response from the host that may be abscess at the inoculation site of diphtheria toxoid counterproductive to viral survival. Furthermore, generated higher specific antibody titers.
establishment of viral latency (absence of viral gene With possible threat of safety issues due to reactogenic expression in the infected host cell) is critical for HIV. How a crude antigen, inclusion of poorly immunogenic purified, virus with a strong promoter can establish and maintain viral subunit or recombinant antigens in modern age vaccine is latency must be examined. Additionally, if the acquisition of becoming more and more frequent. It is thus becoming a stronger viral promoter is necessary for the evolutionary more important that a proper adjuvant should be used in a success, why other subtypes of HIV-1 do not use the same vaccine formulation in order to get the best possible trick for their own success? Moreover, where is the natural outcome in terms of immune response without limit for the gaining of the strength of the viral promoter? We compromising on the safety part. are presently addressing some of these questions. Different adjuvant technologies have been developed. What are the implications for disease management? Mainly used technologies are (1) oil emulsions (oil in water, First of all, our data prove that subtype C possesses water in oil or double emulsions) (2) Mineral salts biological characteristics that make it unique. In other (suchasaluminium hydroxide) (3) Immunostimulant words, variations seen at the genetic level are associated polymers (4) Chemical particles (such as liposomes and with biological differences of the viral subtypes. Second, we nanoparticles) (5) adjuvants from biological origin (such as do not know if the new viral strains of subtype C are likely to saponins, TLR ligands, cytokines). Keeping this fact in mind alter the landscape of the HIV demographics in India and that there is no universal adjuvant, the proper adjuvant other places in the coming years. In the recent past, the rate selection should be the first step to optimize the vaccine of viral expansion has slowed or even declined in several thus it is very important to make a proper adjuvant choice depending on the antigen used in a vaccine formulation in global regions, including India. Our study suggests that the order to have the best balance between safety, efficacy and new viral strains of HIV-1 are more infectious. It remains to stability to get the best possible outcome of vaccine. be determined how the rates of viral prevalence are going to be affected as a consequence of the emerging viral strains Seppic a subsidiary of Air Liquid Group Company has in India and elsewhere. Third, it is possible that the brought onto the market a unique range of vaccine advantages gained by subtype C by developing a stronger adjuvants and has managed to sustain as a world leader in vaccine adjuvant business over past 60 years. Seppic has viral promoter are transmitted to other HIV-1 subtypes developed unique adjuvant technology and takes in to through genetic recombination. Lastly, we do not know if the account several parameters critically affecting the vaccine new HIV-1 strains are likely to promote faster disease performance in order to select the right adjuvant for each vaccine application. Seppic's MONTANIDE range of Our working hypothesis to understand this, we are adjuvants has been very successful worldwide in the planning additional studies. In collaboration with four treatment of every possible species against a pool of viral, Table 1 Percent positivity of commercial kits used for diagnosis of dengue fever different institutions (YRG CARE, Chennai; St. John's bacterial and parasitic diseases. Hospital, Bengaluru; National AIDS Research Institute, With the advancement of molecular mechanism of Pune and All India Institute of Medical Sciences, New disease pathogenesis, it is a proven fact that in addition to Delhi), we will monitor 100 subjects at each site (50 subjects the humoral immunity we need to have more and more cell each with 3- or 4-kB viral infections) for disease progression mediated immune response in order to have effective Fever < 5 days (44) (%) over a period of 2 years. This work supported by the vaccine outcome and better protection coverage against Department of Bio-Technology is to begin soon. Fever > 5 days (42) (%) Total positivity (%) www.ivsnet.in VirusResearch News3(1&2) Page 7 Presently, there are many adjuvants which can induce a population at the face of outbreak and does not recommend cellular response at laboratory level but a very few can be vaccination. However, as part of preparedness for emergency used at the industrial level. Seppic offers a unique situations wherein biosecurity measures alone cannot control innovative range of commercial adjuvants which are ready avian influenza, readiness with a suitable vaccine against to use products and requires no or very less sophistication highly pathogenic H5N1 influenza virus is required. With the for blending at a very large commercial scale for vaccine advent of reverse genetic systems for AI virus, custom made formulation. With the advancement in adjuvant science and inactivated AI vaccines are possible using infectious clones continued research, Seppic could successfully launch new systems. These viruses can be tailored to have same HA type generation adjuvants which can selectively enhance the but different NA type from field strain to allow DIVA cellular immune response without compromising with (differentiation of infected from vaccinated animals) and be humoral immune response which is found to be intact and at rendered safe by altering the hemagglutinin (HA) cleavage the same level. These innovative range of new generation products includes, MONTANIDE ISA 61 VG a water in oil (W/O) for Cattle and Sheep, MONTANIDE ISA 201 VG a We developed a DIVA marker H5N2 inactivated vaccine water in oil in water (W/O/W) for Cattle and Swine and using the rgH5N2 virus (8+2 reassortant) generated. The H5- MONTANIDE ISA 71 VG a water in oil (W/O) for Poultry.
HA gene donor virus was selected from available H5N1 (clade 2.2) viruses through antigenic cartography. The HA-H5 gene In addition to the wide range of adjuvants available for amplified from the selected donor virus A/chicken/West animals, Seppic has also launched its range of vaccine adjuvants for humans with a very high safety profile suitable Bengal/80995/2008(H5N1), was mutated to replace the basic for human injections. It is being widely used in more than amino acid cleavage site (RRRKKR*GLF) with IETR*GLF 150 clinical trials from phase I to phase III in all over the by site directed mutagenesis. A reassortant rgH5N2 virus was world in the domain of therapeutic vaccines, mainly against generated using the 12-plasmid based reverse genetics system cancer, HIV, malaria and autoimmune diseases. The major with the mutated H5-HA and N2-NA gene from H9N2 field human adjuvants are MONTANIDE ISA 51 VG which is isolate (A/chicken/Uttar Pradesh/2543/2004). The rgH5N2 recently approved in a commercial vaccine against lung vaccine candidate virus was found to grow up to 2 HA titre in cancer in humans and MONTANIDE ISA 720 VG which is SPF chicken embryos. The non-pathogenic phenotype and intended against several infectious disease vaccine safety of the rgH5N2 vaccine candidate virus was validated by applications in human. Both these adjuvants are DMF intravenous pathogenicity test and intranasal challenge test. available, multicompendial product and can be seen for The protective efficacy of the inactivated rgH5N2 vaccine was regulated market vaccine business.
shown to be 100% against high dose challenge with HPAI bird) in vaccinated chickens with single vaccination (0.5 ml/bird) on 28 day post-vaccination (Fig.1). The vaccinated birds showed high level of anti-H5 antibody SEPPIC: World leader of ready response estimated by HI test (>2 ). Challenge virus shedding to use adjuvants for veterinary via oro-pharynx of the vaccinated chickens, estimated by real and human vaccines time RT-PCR, was found to be at minimal detectable level on 1 and 3 day post challenge. In another experiment, a single dose vaccinated chickens showed high HI titres (>2 ) which was maintained without booster vaccination at least till 5 months. The work has established India's self-sufficiency to generate re-assortant influenza viruses through use of reverse genetics for making DIVA marker avian influenza vaccines and to carry out other important studies on avian influenza virus. This work was conducted under National Fellow project funded by Education Division of ICAR. New vaccine for highly pathogenic Avian Influenza (H5N1)Sandeep BhatiaOIE Reference Expert for Avian InfluenzaNational Institute of High Security Animal Diseases, Anand Nagar, Bhopal - 462 021, INDIA ([email protected]) Fig.1. The SPF chicken administered with inactivated rgH5N2 vaccine For the control of avian influenza in poultry, India follows remained healthy, whereas the control group died within 24-96 h of a policy of elimination of infected and susceptible avian challenge of the virus.
www.ivsnet.in VirusResearch News3(1&2) Page 8 Ebola epidemic 2014: An international concern to human contact transmission of the virus. Transmission occurs via blood or bodily fluids from the infected person or by the contact with the objects contaminated by the virus, particularly needles and syringes. The initial phase of the Ebola disease includes the flu like symptoms such as fatigue, fever, headaches, joint, muscle, and abdominal pain. The initial phase is followed by the bleeding phase, which begins at Shailendra K. Saxena 5-7 days after the first symptoms, which is characterized by CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, internal and subcutaneous bleeding in the form of reddened Hyderabad 500007, India ([email protected]) eyes and hematemesis (blood vomiting), followed by heavy bleeding of the gastrointestinal tract etc. As there are no initial Currently various countries in Africa, including Liberia, Sierra typical clinical symptoms for the EVD, it is difficult to Leone, and Guinea, are facing disaster due to Ebola virus distinguish the disease from the other infectious disease such disease (EVD) with at least 17,800 cumulative cases and 6,331 as malaria, typhoid fever and meningitis. The disease is deaths. EVD, Ebola hemorrhagic fever (EHF) or simply Ebola diagnosed Isolating the virus by cell culture, detecting its RNA is a serious fatal illness caused by the Ebola virus of family or proteins by PCR and ELISA, or detecting antibodies Filoviridae. The first evidence of the Ebola was dated in 1976, in specific for viral antigens in a person's blood. Genome or gene two places simultaneously, one in Nzara, Sudan, and the other sequence is used for the efficient identification of the virus and in Yambuku, Democratic Republic of Congo. The latter one also strain identification. occurred in the village near the Ebola River, thus the name given to the virus. Since then there are the reported cases of the No vaccine/specific treatment for the EVD are approved chronological outbreaks of the Ebola in the various African by the Food and Drug Administration (FDA, USA) till now. countries (CDC). Recent outbreak in 2014 is supposed to be the Treatment of the Ebola is symptomatic and early supportive largest outbreak considering the highest number of cases and care with rehydration can increase the survival rate. Several deaths compared to all previous outbreaks. Primates and fruit treatment measures such as packed red blood cells, platelets or bats are the natural hosts for the EVD. fresh frozen plasma, regulators of coagulation have also been tried including heparin in an effort to prevent intravascular The current Ebola outbreak is generally due to the human blood clotting and clotting factors to reduce bleeding are Prof. K.S. Bhargava Oration Award
Prof. Narayan Rishi 3. Dr. Basavaprabhu L. Patil Amity University, Noida National Research Center on Plant Biotechnology, New Delhi FELLOW of IVS
4. Dr. R. Viswanathan Sugarcane Breeding Institute, Coimbatore Animal Virology
1. Dr. Ashok K. Tiwari
Indian Veterinary Research Institute, 5. Dr. Shailendra K. Saxena Centre for Cellular and Molecular Biology, Hyderabad 2. Dr. Yashpal S. Malik 6. Dr. Yogesh K Chawala Indian Veterinary Research Institute, Post-Graduate Institute of Medical Institute of Medical Education and Research, Chandigarh Submit news article, which has some application prospect to Dr. Bikash Mandal, [email protected] any one of the editors. The article to be written in a popular format not exceeding 1000 words with a few simple table and Dr. Suresh Mahalingam, Medical Virology, or high quality figures. Article structure: Title, author(s), full address, email, telephone, self photo of corresponding Dr. Arvind Rai, Medical Virology, [email protected]. Rajeev kaul, Medical Virology, [email protected] author, running text.
Dr. YPS Malik, Veterinary Virology, [email protected]. V. Balamurugan, Veterinary Virology, [email protected] Dr. B.L. Patil, Plant Virology, [email protected]. K.V. Rajendran, Fishery Virology, [email protected] INDIAN VIROLOGICAL SOCIETY
Ex-officio members F-3, A-Block, National Societies Block, Prof. Anil Prasad, President, IVS, [email protected] NASC Complex, D.P.S. Marg, Pusa, New Delhi – 110 012, Dr. G.P. Rao, Secretary, IVS, [email protected] India, Tel: +91-9711763384 Editorial ManagerDr. Naveen Pandey E-mail: [email protected], website: www.ivsnet.in applied. However, there is no evidence that these methods are significant for the treatment. Recombinant vaccines has evoked good levels of immunity in case of knock-out mouse but also the antibody response in interferon knock-out mouse was similar to vaccinated wild-type mice. A wide variety of investigational drugs are being tested for the treatment against the Ebola, but all of them are yet in the level of clinical trial in animals or further. The outbreak of the 2014 has proposed a great risk. The prime focus must be given on the development of reliable diagnostics, vaccine and therapeutic drugs. Health education must be provided in the areas having the outbreak to prevent further spreading of the virus. If optimum precautions are not taken then this outbreak may result into another historic epidemic of mankind.

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– summarising clinical guidelines for primary care Endorsed by Symptomatic management of multiple sclerosis in primary care This guideline was developed by a multidisciplinary expert panel: Rashid W et al with the support of a grant from both Bayer Healthcare and Novartis. The Multiple Sclerosis Society has endorsed this working party guideline. See inside front cover for full disclaimer.

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NICOTINE AND DRUG INTERACTIONS lung physician Tartu University Lung Clinic ABRUPT SMOKING CESSATION CAN AFFECT THE METABOLISM OF DRUGS.  When patients enter hospital they may have to stop smoking abruptly if the hospital has a ‘no smoking' policy.  Cigarette smoking induces the activity of human cytochromes P450 (CYP) 1A2 and 2B6.  Decreased CYP1A2 activity after smoking cessation