Circulation of a single hepatitis A virus genotype IIIA with two distinct clusters in different states of India.

With the changing hepatitis A epidemiology in India, focal viral outbreaks are being reported from different parts of the country. This study presents Hepatitis A Virus (HAV) strain characterization (period 2009-2020) from 18 states of India. For that, blood and stool samples (n â€‹= â€‹280) were screened for HAV RNA and sequences for 5'non-coding and VP3 regions were generated from positive samples (n â€‹= â€‹68). Presence of a single IIIA genotype in all samples indicated IIIA being the only HAV genotype currently circulating in India. Interestingly, it was evident that these strains form two distinct groups suggesting independent evolution of these two clusters.

Envelope specific T cell responses & cytokine profiles in chikungunya patients hospitalized with different clinical presentations.

BACKGROUND & OBJECTIVES: Since the 2006 massive outbreaks, chikungunya (CHIK) is a major public health concern in India. The aim of this study was to assess envelope specific immune responses in patients with chikungunya infection. METHODS: This study included 46 hospitalized patients with chikungunya virus infection (encephalitis, n=22, other systemic involvement, OSI, n=12, classical, n=12) and six controls from Ahmedabad city, Gujarat, India. T cell responses and the levels of Th1, pro/ anti-inflammatory cytokines against the CHIK virus envelope antigens were assessed by lymphocyte proliferation assay and by cytometric bead array in flow cytometry, respectively. RESULTS: Lymphoproliferative response was uniform among the patients. Comparisons of cytokines revealed significantly higher levels of interleukin (IL)-4 and IL-5 in encephalitis, OSI and classical patients versus controls. The levels of tumour necrosis factor (TNF)-α were higher in classical patients categories compared to the controls. Interferon (IFN)-γ levels were lower in encephalitis patients versus control. INTERPRETATION & CONCLUSIONS: Our findings showed recognition of T cell epitopes on the envelope region of chikungunya virus by all patient categories. Lower level of IFN-γ may be associated with the severity of disease in these patients.

Expression profile of immune response genes during acute myopathy induced by chikungunya virus in a mouse model.

During the recent re-emergence of chikungunya, clinical complications and deaths were recorded. Persistent musculoskeletal pain, arthralgia, arthritis were among the most common complications. To understand pathogenesis of CHIKV induced disease, we developed suckling, outbred mouse model presenting with severe myopathology. Histopathology, dynamics of viral load, IgG antibodies/isotypes, serum cytokines by cytometric bead array and mRNA expression levels of immune response genes in the target tissue by Taqman Low Density Array were studied. Peak viral load was associated with peak serum levels of CCL-2,KC, CCL-4, RANTES, IL-6, IL-10, CSF-3, and locally very high mRNA expression of CCL-2, CXCL-10, CXCL-11 and concomitant IFNγ, IL-10, STAT-1, SOCS-1 and CSF-3 suggesting strong IFNγ program. Symptomatic phase correlated with peak serum levels of IL-2, IFNγ, IL-17, CCL-3, IL-1ß, eotaxin, IL-9 and CSF-2 and locally with peak mRNA expression of macrophage induced pro inflammatory cytokines and immune infiltration biased towards Th1. IgG antibodies were detected on day 6PI, reaching high titres by day 11PI. IgG2a was the predominant isotype, indicating Th1 bias. This is the first report of comprehensive analysis of immune response genes expression in target tissue of CHIKV mouse model. The data would contribute significantly in understanding pathogenesis of CHIKV disease and viral myopathies.

Evolutionary rates and timescale comparison of Chikungunya viruses inferred from the whole genome/E1 gene with special reference to the 2005-07 outbreak in the Indian subcontinent.

Chikungunya (CHIK) virus reemerged during 2005-07 as an important pathogen causing massive disease outbreaks affecting India and several countries of the Indian Ocean. Knowledge of the evolutionary rates and divergence times of the CHIK virus may help to better understand the disease epidemiology. Considering the limited availability of such information, we estimated the substitution rates and the ancestral times for all the CHIK genotypes and also the time to the most recent common ancestor (tMRCA) of the 2005-07 isolates. Using whole genomes and partial E1 gene datasets, we applied the Bayesian Markov Chain Monte Carlo (MCMC) framework that explicitly accounts for lineage-specific evolutionary rates through the use of 'relaxed' molecular clock models. Under a constant population relaxed clock model, the evolutionary timescale of CHIK viruses in this study was estimated to be in the last 300 years. The progenitor of the 2005-07 viruses was found to have existed around 9 years ago, and to have originated from Central Africa. The presence of a strain in India in 2000 that bears 99% identity with a Ugandan strain of 1982, which correlates with the tMRCA of the Indian and Indian Ocean isolates, confirms our earlier report that the progenitor of the 2005-07 isolates originates from Uganda's neighbourhood. The 'A226V' mutation that existed in the Indian Ocean isolates since late 2005 was found to occur only in the 2007 isolate from India. The study confirms the epidemiological data, specifically with regard to the re-emergence of CHIKV and throws light on the evolutionary dynamics of CHIK viruses.

Chikungunya outbreaks caused by African genotype, India.

Chikungunya fever is reported in India after 32 years. Immunoglobulin M antibodies and virus isolation confirmed the cause. Phylogenic analysis based on partial sequences of NS4 and E1 genes showed that all earlier isolates (1963-1973) were Asian genotype, whereas the current and Yawat (2000) isolates were African genotype.