Enterovirus Research Center

Mumbai, India

Enterovirus Research Center

Mumbai, India
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Bessaud M.,Aix - Marseille University | Razafindratsimandresy R.,Institute Pasteur Of Madagascar | Nougairede A.,Aix - Marseille University | Joffret M.-L.,Institute Pasteur Paris | And 9 more authors.
PLoS ONE | Year: 2014

Most circulating strains of Human enterovirus 71 (EV-A71) have been classified primarily into three genogroups (A to C) on the basis of genetic divergence between the 1D gene, which encodes the VP1 capsid protein. The aim of the present study was to provide further insights into the diversity of the EV-A71 genogroups following the recent description of highly divergent isolates, in particular those from African countries, including Madagascar. We classified recent EV-A71 isolates by a large comparison of 3,346 VP1 nucleotidic sequences collected from GenBank. Analysis of genetic distances and phylogenetic investigations indicated that some recently-reported isolates did not fall into the genogroups A-C and clustered into three additional genogroups, including one Indian genogroup (genogroup D) and 2 African ones (E and F). Our Bayesian phylogenetic analysis provided consistent data showing that the genogroup D isolates share a recent common ancestor with the members of genogroup E, while the isolates of genogroup F evolved from a recent common ancestor shared with the members of the genogroup B. Our results reveal the wide diversity that exists among EV-A71 isolates and suggest that the number of circulating genogroups is probably underestimated, particularly in developing countries where EV-A71 epidemiology has been poorly studied. © 2014 Bessaud et al.


Hovi T.,Finnish National Institute for Health and Welfare | Shulman L.M.,Sheba Medical Center | Van Der Avoort H.,National Institute of Public Health and the Environment RIVM | Deshpande J.,Enterovirus Research Center | And 2 more authors.
Epidemiology and Infection | Year: 2012

Environmental poliovirus surveillance (ENV) means monitoring of poliovirus (PV) transmission in human populations by examining environmental specimens supposedly contaminated by human faeces. The rationale is based on the fact that PV-infected individuals, whether presenting with disease symptoms or not, shed large amounts of PV in the faeces for several weeks. As the morbidity: infection ratio of PV infection is very low, this fact contributes to the sensitivity of ENV which under optimal conditions can be better than that of the standard acute flaccid paralysis (AFP) surveillance. The World Health Organization has included ENV in the new Strategic Plan of the Global Polio Eradication Initiative for years 2010-2012 to be increasingly used in PV surveillance, supplementing AFP surveillance. In this paper we review the feasibility of using ENV to monitor wild PV and vaccine-derived PV circulation in human populations, based on global experiences in defined epidemiological situations. © 2011 Cambridge University Press and World Health Organization.


PubMed | Enterovirus Research Center, Korean International Vaccine Institute, Indian National Institute of Cholera and Enteric Diseases and World Health Organization
Type: Clinical Trial | Journal: PloS one | Year: 2016

The gold standard for assessing mucosal immunity after vaccination with poliovirus vaccines consists in measuring virus excretion in stool after challenge with oral poliovirus vaccine (OPV). This testing is time and resource intensive, and development of alternative methods is a priority for accelerating polio eradication. We therefore evaluated circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immunity to poliovirus vaccine.199 subjects, aged 10 years, and previously immunized repeatedly with OPV, were selected. Subjects were assigned to receive either a booster dose of inactivated poliovirus vaccine (IPV), bivalent OPV (bOPV), or no vaccine. Using a micro-modified whole blood-based ELISPOT assay designed for field setting, circulating poliovirus type-specific IgA- and IgG-ASCs, including gut homing 47+ ASCs, were enumerated on days 0 and 7 after booster immunization. In addition, serum samples collected on days 0, 28 and 56 were tested for neutralizing antibody titers against poliovirus types 1, 2, and 3. Stool specimens were collected on day 28 (day of bOPV challenge), and on days 31, 35 and 42 and processed for poliovirus isolation.An IPV dose elicited blood IgA- and IgG-ASC responses in 84.8 to 94.9% of subjects, respectively. In comparison, a bOPV dose evoked corresponding blood ASC responses in 20.0 to 48.6% of subjects. A significant association was found between IgA- and IgG-ASC responses and serum neutralizing antibody titers for poliovirus type 1, 2, 3 (p<0.001). In the IPV group, 47+ ASCs accounted for a substantial proportion of IgA-ASCs and the proportion of subjects with a positive 47+ IgA-ASC response to poliovirus types 1, 2 and 3 was 62.7%, 89.8% and 45.8%, respectively. A significant association was observed between virus excretion and 47+ IgA- and/or IgG-ASC responses to poliovirus type 3 among immunized children; however, only a weak association was found for type 1 poliovirus.Our results suggest that virus-specific blood ASCs, especially for type 3 poliovirus, can serve as surrogate of mucosal immunity after vaccination. Further studies are needed to evaluate the duration of such memory responses and to assess the programmatic utility of this whole blood-based mucosal ASC testing for the polio eradication program.


Sutter R.W.,World Health Organization | John T.J.,India Expert Advisory Group on Polio Eradication | Jain H.,Mahatma Gandhi Memorial Medical College | Agarkhedkar S.,Dr D y Patil Medical College | And 10 more authors.
The Lancet | Year: 2010

Poliovirus types 1 and 3 co-circulate in poliomyelitis-endemic countries. We aimed to assess the immunogenicity of a novel bivalent types 1 and 3 oral poliovirus vaccine (bOPV). We did a randomised, double-blind, controlled trial to assess the superiority of monovalent type 2 OPV (mOPV2), mOPV3, or bOPV over trivalent OPV (tOPV), and the non-inferiority of bivalent vaccine compared with mOPV1 and mOPV3. The study was done at three centres in India between Aug 6, 2008, and Dec 26, 2008. Random allocation was done by permuted blocks of ten. The primary outcome was seroconversion after one monovalent or bivalent vaccine dose compared with a dose of trivalent vaccine at birth. The secondary endpoints were seroconversion after two vaccine doses compared with after two trivalent vaccine doses and cumulative two-dose seroconversion. Parents or guardians and study investigators were masked to treatment allocation. Because of multiple comparisons, we defined p≤0·01 as statistically significant. This trial is registered with Current Controlled Trials, ISRCTN 64725429. 900 newborn babies were randomly assigned to one of five vaccine groups (about 180 patients per group); of these 70 (8) discontinued, leaving 830 (92) for analysis. After the first dose, seroconversion to poliovirus type 1 was 20 for both mOPV1 (33 of 168) and bOPV (32 of 159) compared with 15 for tOPV (25 of 168; p>0·01), to poliovirus type 2 was 21 (35 of 170) for mOPV2 compared with 25 (42 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 12 (20 of 165) for mOPV3 and 7 (11 of 159) for bOPV compared with 4 (7 of 168) for tOPV (mOPV3 vs tOPV p=0·01; bOPV vs tOPV; p>0·01). Cumulative two-dose seroconversion to poliovirus type 1 was 90 (151 of 168) for mOPV1 and 86 (136 of 159) for bOPV compared with 63 (106 of 168) for tOPV (p<0·0001), to poliovirus type 2 was 90 (153 of 170) for mOPV2 compared with 91 (153 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 84 (138 of 165) for mOPV3 and 74 (117 of 159) for bOPV compared with 52 (87 of 168) for tOPV (p<0·0001). The vaccines were well tolerated. 19 serious adverse events occurred, including one death; however, these events were not attributed to the trial interventions. The findings show the superiority of bOPV compared with tOPV, and the non-inferiority of bOPV compared with mOPV1 and mOPV3. GAVI Alliance, World Health Organization, and Panacea Biotec. © 2010 Elsevier Ltd.


Shetty S.A.,Enterovirus Research Center | Mathur M.,Lokmanya Tilak Medical College and Hospital | Deshpande J.M.,Enterovirus Research Center
Journal of Medical Microbiology | Year: 2014

Hospital-based rotavirus surveillance was carried out in Mumbai during 2005-2009. An isolate (B08299) with a rare genotype combination (G11P[25]) was detected. The present study was undertaken to characterize the complete genome of the isolate. B08299 exhibited a G11-P[25]-I12-R1-C1-M1-A1-N1-T1-E1-H1 genotype constellation. Phylogenetic analysis of the 11 gene segments of B08299 revealed that the VP2 and NSP5 genes of B08299 had a human origin, while the VP6 gene represented an I12 genotype of obscure origin. The remaining six genes formed a lineage distinct from human and porcine rotaviruses within genotype 1. Analysis of the structural and non-structural genes suggested that B08299 has evolved by gene reassortment. Our findings provide further evidence that interspecies transmission is an important mechanism involved in the evolution and genetic diversity of human rotaviruses in nature. © 2014 The Authors.


De Silva R.,Medical Research Institute | Gunasena S.,Medical Research Institute | Ratnayake D.,Medical Research Institute | Wickremesinghe G.D.,Medical Research Institute | And 5 more authors.
Vaccine | Year: 2012

Background: The Global Polio Eradication Initiative, established in 1988, has made substantial progress toward achieving this target, with only 3 countries never having eliminated wild poliovirus. Persons with primary immune deficiency disorders (PIDD) exposed to OPV are at increased risk of vaccine-associated paralytic poliomyelitis (VAPP) and of prolonged excretion of Sabin polioviruses. However, the risk for prolonged excretion is not known. Therefore, we studied the prevalence of PIDD with long-term poliovirus excretion in Sri Lanka, a middle income country currently using OPV. Methods: We stimulated the referral of patients under the age of 35 years, with clinical features suggestive of immune deficiency to the single immunology clinic in the country, where these patients were investigated for the presence of PIDD. Stool samples from patients with PIDD were cultured for the presence of poliovirus (PV). Poliovirus isolates were tested for intratypic differentiation (ITD). The VP1 region of all poliovirus isolates was sequenced. Results: Of 942 patients investigated, 51 (5.4%) were diagnosed with PIDD. Five (10.2%) patients excreted poliovirus. A patient with X linked agammaglobulinemia (XLA) excreted a mixture of all three Sabin like (SL) poliovirus serotypes. One patient with severe combined immune deficiency (SCID) excreted SL type 2, and another with SCID excreted SL type 3. One patient with SCID excreted a P2 vaccine-derived poliovirus (VDPV 2), and another with common variable immune deficiency (CVID) excreted a VDPV 3. The 3 patients with SCID died before scheduled collection of subsequent samples one month later, while the patient with XLA had cleared the virus in stool sample collected after 3 and 11 months. The CVID patient with VDPV 3 excreted for 7 months, and has developed a 23 nucleotide divergence in VP1 (∼900 nucleotides) from the parental Sabin virus. Conclusions: In our study, several patients with SCID, XLA and CVID excreted poliovirus. With improving health care quality patients with CVID and XLA may survive longer especially with provision of intravenous immune globulin. Regular screening of patients with PIDD for excretion of poliovirus is necessary to identify chronic excretors and make available specific therapies. © 2012 Elsevier Ltd.


Saxena V.K.,Enterovirus Research Center | Sane S.,Jupiter Hospital | Nadkarni S.S.,Enterovirus Research Center | Sharma D.K.,Enterovirus Research Center | Deshpande J.M.,Enterovirus Research Center
Emerging Infectious Diseases | Year: 2015

We have identified circulation of 3 genogroups of enterovirus (EV) A71 in India. A new genogroup (proposed designation G) was discovered during this study. We isolated genogroups D and G in wide geographic areas but detected subgenogroup C1 only in 1 focus in western India. A systematic nationwide search for EV-A71 is warranted. © 2015, Centers for Disease Control and Prevention (CDC). All rights reserved.


Mohanty M.C.,Enterovirus Research Center | Deshpande J.M.,Enterovirus Research Center
Indian Journal of Medical Research | Year: 2013

Background & objectives: Polioviruses are the causative agent of paralytic poliomyelitis. Attenuated polioviruses (Sabin oral poliovirus vaccine strains) do not replicate efficiently in neurons as compared to the wild type polioviruses and therefore do not cause disease. This study was aimed to investigate the differential host immune response to wild type 1 poliovirus (wild PV) and Sabin attenuated type 1 poliovirus (Sabin PV) in cultured human neuronal cells. Methods: By using flow cytometry and real time PCR methods we examined host innate immune responses and compared the role of toll like receptors (TLRs) and cytoplasmic RNA helicases in cultured human neuronal cells (SK-N-SH) infected with Sabin PV and wild PV. Results: Human neuronal cells expressed very low levels of TLRs constitutively. Sabin PV infection induced significantly higher expression of TLR3, TLR7 and melanoma differentiation-associated protein-5 (MDA-5) m-RNA in neuronal cells at the beginning of infection (up to 4 h) as compared to wild PV. Further, Sabin PV also induced the expression of interferon α/β at early time point of infection. The induced expression of IFN α/β gene by Sabin PV in neuronal cells could be suppressed by inhibiting TLR7. Interpretation & conclusions: Neuronal cell innate immune response to Sabin and wild polioviruses differ significantly for TLR3, TLR7, MDA5 and type 1 interferons. Effects of TLR7 activation and interferon production and Sabin virus replication in neuronal cells need to be actively investigated in future studies.


Sharma D.K.,Enterovirus Research Center | Nalavade U.P.,Enterovirus Research Center | Deshpande J.M.,Enterovirus Research Center
Indian Journal of Medical Research | Year: 2015

Background & objectives: The poliovirus serotype identification and intratypic differentiation by real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay is suitable for serotype mixtures but not for intratypic mixtures of wild and vaccine poliovirus strains. This study was undertaken to develop wild poliovirus 1 and 3 (WPV1 and WPV3) specific rRT-PCR assays for use. Methods: Specific primers and probes for rRT-PCR were designed based on VP1 sequences of WPV1 and WPV3 isolated in India since 2000. The specificity of the rRT-PCR assays was evaluated using WPV1 and WPV3 of different genetic lineages, non-polio enteroviruses (NPEVs) and mixtures of wild/wild and wild/Sabin vaccine strains. The sensitivity of the assays was determined by testing serial 10-fold dilutions of wild poliovirus 1 and 3 stock suspensions of known titre. Results: No cross-reactivity with Sabin strains, intertypic wild poliovirus isolates or 27 types of NPEVs across all the four Enterovirus species was found for both the wild poliovirus 1 and 3 rRT-PCR assays. All WPV1 and WPV3 strains isolated since 2000 were successfully amplified. The rRT-PCR assays detected 104.40CCID50/ml of WPV1 and 104.00CCID50/ml of WPV3, respectively either as single isolate or mixture with Sabin vaccine strains or intertypic wild poliovirus. Interpretation & conclusions: rRT-PCR assays for WPV1 and WPV3 have been validated to detect all the genetic variations of the WPV1 and WPV3 isolated in India for the last decade. When used in combination with the current rRT-PCR assay testing was complete for confirmation of the presence of wild poliovirus in intratypic mixtures. © 2015, Indian Council of Medical Research. All rights reserved.


PubMed | Enterovirus Research Center
Type: Journal Article | Journal: The Indian journal of medical research | Year: 2016

It is important to understand the role of cell surface receptors in susceptibility to infectious diseases. CD155 a member of the immunoglobulin super family, serves as the poliovirus receptor (PVR). Heterozygous (Ala67Thr) polymorphism in CD155 has been suggested as a risk factor for paralytic outcome of poliovirus infection. The present study pertains to the development of a screening test to detect the single nucleotide (SNP) polymorphism in the CD155 gene.New primers were designed for PCR, sequencing and SNP analysis of Exon2 of CD155 gene. DNAs extracted from either whole blood (n=75) or cells from oral cavity (n=75) were used for standardization and validation of the SNP assay. DNA sequencing was used as the gold standard method.A new SNP assay for detection of heterozygous Ala67Thr genotype was developed and validated by testing 150 DNA samples. Heterozygous CD155 was detected in 27.33 per cent (41/150) of DNA samples tested by both SNP detection assay and sequencing.The SNP detection assay was successfully developed for identification of Ala67Thr polymorphism in human PVR/CD155 gene. The SNP assay will be useful for large scale screening of DNA samples.

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