Immune response during acute Chandipura viral infection in experimentally infected susceptible mice

<p>Abstract</p> <p>Background</p> <p>Age dependent susceptibility was observed in Chandipura virus (CHPV) infected mice through intravenous and intraperitoneal route. Adult mice were susceptible only through intracerebral route of infection. Immature neuron and some other biological variables including immature immune system are considered to be important factor for age related susceptibility in some diseases. As Chandipura virus infects both young and adult mice brain through intracerebral route the role of immune system during peripheral infection in young susceptible mice needs to be studied.</p> <p>Results</p> <p>Through intravenous route of infection the virus produces vireamia and cross the blood brain barrier (BBB) to replicate in the central nervous system. Circulating virus is effectively cleared by virus specific IgM antibody but replication in CNS continues. The infected mice secreted significant amount of proinflammatory cytokines like TNFα and MCP-1 and high amount of IFNγ, IL-1 and IL-6 at 24 h post infection. Reduction in significant amount of CD4, CD8 and CD19 positive cells at 72 h post infection (p < 0.000) was observed in infected mice. Suppression of T cell proliferation of splenocytes to Con A (p < 0.000), LPS and specific antigen was also observed. Presence of preformed virus specific antibody in the form of passive immunization completely protected the mice but immunization on the day or after the virus infection could not completely protect the mice.</p> <p>Conclusion</p> <p>Proinflammatory cytokines at 24 h post infection and reduction of CD4, CD8 and CD19 positive immune cells might make the mice immune compromised during infection. These cytokines might also increase the permeability of BBB to allow the virus to enter into CNS. Virus replication in CNS is responsible for neurological symptom and mortality. Once virus gets established in CNS it is difficult to protect the mice by passive immunization.</p

Immune regulation in Chandipura virus infection: characterization of CD4+ T regulatory cells from infected mice

<p>Abstract</p> <p>Back ground</p> <p>Chandipura virus produces acute infection in mice. During infection drastic reduction of CD4+, CD8+ and CD19 + cell was noticed. Depletion of lymphocytes also noticed in spleen. The reduction may be due to the regulatory mechanism of immune system to prevent the bystander host tissue injury. There are several mechanisms like generation of regulatory cells, activation induced cell death (ACID) etc were indicated to control the activation and maintain cellular homeostasis. Role of regulatory cells in homeostasis has been described in several viral diseases. This study was undertaken to characterize CD4+T regulatory cells from the infected mice.</p> <p>Method</p> <p>In this study we purified the CD4+ T cells from Chandipura virus infected susceptible Balb/c mice. CD4+ T regulatory cells were identified by expression of cell surface markers CD25, CD127 and CTLA-4 and intracellular markers Foxp3, IL-10 and TGF-beta. Antigen specificity and ability to suppress the proliferation of other lymphocytes were studied <it>in vitro </it>by purified CD4+CD25+T regulatory cells from infected mice. The proliferation was calculated by proliferation module of Flow Jo software. Expression of death receptors on regulatory cells were studied by flowcytometer.</p> <p>Results</p> <p>The CD4+ T cells isolated from infected mice expressed characteristic markers of regulatory phenotype at all post infective hours tested. The CD4+ T regulatory cells were proliferated when stimulated with Chandipura virus antigen. The regulatory cells did not suppress the proliferation of splenocytes stimulated with anti CD3 antibody when co cultured with them. Interesting observation was, while purification of CD4+ T cells by negative selection, the population of cells negative for CD4 also co purified along with CD4+ T cell. Flow cytometry analysis and light microscopy revealed that CD4 negative cells were of different size and shape (atypical) compared to the normal lymphocytes. Greater percentage of these atypical lymphocytes expressed <it>Fas </it>Ligand and Programmed Death1 (PD-1) receptor.</p> <p>Conclusion</p> <p>From these results we concluded that virus specific CD4+T regulatory cells are generated during Chandipura virus infection in mice and these cells might control the activated lymphocytes during infection by different mechanism.</p

Chandipura Virus’ Oncolytic Potential in Experimentally Induced Tumor in Mice

Chandipura virus (CHPV) is a tropical pathogen, suggesting its involvement in childhood encephalitis syndrome in India. No reports are available in adult human beings for its pathogenicity. Similarly, in adult mice, the virus does not develop pathogenesis by parenteral route except for intracranial route of infection. The virus is remarkably nonpathogenic to adult immunocompromised nude mice. In vitro in tissue culture, the CHPV infects and kills many types of cells. All of these properties could qualify the CHPV to be a candidate virus for tumor therapy. To prove this, an experimentally induced tumor in a mouse was infected with live CHPV. The results showed that intra-tumoral injection reduced the volume of tumor and increased the longevity of the mice. The study concludes that the CHPV may be a safe tumor therapy virus. More precisely, the discovery of CHPV protein with oncolytic potential may lead to the development of novel drugs/therapeutics. </jats:p

Identification of Dengue Serotypes using a Single Serum Specimen Algorithm in a Tertiary Care Hospital, Alappuzha, Kerala, India

Introduction: The geographic location of Alappuzha, a district in the South Indian state of Kerala, the distinct weather conditions and frequent natural calamities present a unique ecology that contributes to the prevalence of vector-borne diseases like dengue. Early dengue virus infection can be detected by using a combination of tests on a single serum specimen. Aim: To identify the dengue virus serotypes among hospitalised patients in a South Indian teaching hospital in Alappuzha, Kerala, India. Materials and Methods: Patient samples that tested positive for dengue non-structural protein-1 (NS1) antigen by ELISA were further evaluated for dengue virus RNA by real-time, multiplex reverse transcriptase Polymerase Chain Reaction (PCR) and the serotype was determined. Anonymised patient data was collected using a questionnaire as a data collection tool. The data was analysed for statistical significance. Results: Among 422 non-duplicate patient serum samples received in the Department of Microbiology, in the year 2019, 30 were positive for dengue NS1 antigen by ELISA. Dengue viral RNA was detected in 50% of the samples (15/30). DENV-3 serotype was the most prevalent (nine) followed by DENV-1 (five) and DENV-2 (one). Common presentations of the patients were fever, headache, and myalgia. No statistically significant association was found between a PCR positive result and the presence of warning signs and thrombocytopenia. Conclusion: DENV-3 was the most common serotype in the study population. Early dengue virus infection is associated with varied symptoms.</jats:p

Complete Genome Sequence of West Nile Virus Isolated from Alappuzha District, Kerala, India

ABSTRACT West Nile virus belongs to the Flaviviridae family, transmitted by vector mosquitoes. Here, we reported the complete genome sequence of West Nile virus isolated from human samples during an acute encephalitis outbreak in Kerala, India. Phylogenetic analysis revealed that the virus genome clusters into genetic lineage 1, clade 1a. </jats:p