Human enteric adenovirus (HAdV) belonging to species F is one of the most common pathogens responsible for infantile gastroenteritis worldwide. This study was initiated to estimate prevalence and types of HAdV among children below 5 years of age seeking health care facility for treatment of diarrhea in Kolkata, Eastern India. A total of 1,562 stool specimens were tested during 2013-2014 and among them, 185 (11.8%) were positive for enteric HAdV. Maximum number of positive cases were observed among children between 6 and 12 months of age (13.9%). HAdV infection occurred at a low frequency throughout the year, with an increased incidence in the month of March-July in both the years. Among HAdV positive samples (n = 185), 44.8% showed coinfection with rotavirus. Genotyping based on hypervariable region of hexon and partial shaft region of fiber genes, revealed prevalence of HAdV-40 over HAdV-41 genotype during this study period. Nucleotide sequence analysis of HAdV-40 strains exhibited more than 99% similarity among themselves and 98.5% with the prototype strain Dugan. Sequence analysis of six hypervariable regions (HVRs) of hexon genes from all the HAdV-41 strains revealed co-circulation of both genome type cluster 1(GTC1) and GTC2. The presence of both types of GTCs reflects accumulation of amino acid (aa) mutations in HVR of hexon gene. A recombination event was evident in a subset of HAdV-41 strains where hexon gene belonged to GTC1 whereas, fiber gene clustered with GTC2. Sequence analysis of fiber gene shaft region of HAdV-41 strains revealed 15 aa deletion from the 15th repeat motif. J. Med. Virol. 89:606-614, 2017. © 2016 Wiley Periodicals, Inc.

Accumulation of mutations within the genome is the primary driving force in viral evolution within an endemic setting. This inherent feature often leads to altered virulence, infectivity and transmissibility, and antigenic shifts to escape host immunity, which might compromise the efficacy of vaccines and antiviral drugs. Therefore, we carried out a genome-wide analysis of circulating SARS-CoV-2 strains to detect the emergence of novel co-existing mutations and trace their geographical distribution within India. Comprehensive analysis of whole genome sequences of 837 Indian SARS-CoV-2 strains revealed the occurrence of 33 different mutations, 18 of which were unique to India. Novel mutations were observed in the S glycoprotein (6/33), NSP3 (5/33), RdRp/NSP12 (4/33), NSP2 (2/33), and N (1/33). Non-synonymous mutations were found to be 3.07 times more prevalent than synonymous mutations. We classified the Indian isolates into 22 groups based on their co-existing mutations. Phylogenetic analysis revealed that the representative strains of each group were divided into various sub-clades within their respective clades, based on the presence of unique co-existing mutations. The A2a clade was found to be dominant in India (71.34%), followed by A3 (23.29%) and B (5.36%), but a heterogeneous distribution was observed among various geographical regions. The A2a clade was highly predominant in East India, Western India, and Central India, whereas the A2a and A3 clades were nearly equal in prevalence in South and North India. This study highlights the divergent evolution of SARS-CoV-2 strains and co-circulation of multiple clades in India. Monitoring of the emerging mutations will pave the way for vaccine formulation and the design of antiviral drugs.

Accumulation of mutations within the genome is the primary driving force for viral evolution within an endemic setting. This inherent feature often leads to altered virulence, infectivity and transmissibility as well as antigenic shift to escape host immunity, which might compromise the efficacy of vaccines and antiviral drugs. Therefore, we aimed at genome-wide analyses of circulating SARS-CoV-2 viruses for the emergence of novel co-existing mutations and trace their spatial distribution within India. Comprehensive analysis of whole genome sequences of 441 Indian SARS-CoV-2 strains revealed the occurrence of 33 different mutations, 21 being distinctive to India. Emergence of novel mutations were observed in S glycoprotein (7/33), NSP3 (6/33), RdRp/NSP12 (4/33), NSP2 (2/33) and N (2/33). Non-synonymous mutations were found to be 3.4 times more prevalent than synonymous mutations. We classified the Indian isolates into 22 groups based on the co-existing mutations. Phylogenetic analyses revealed that representative strain of each group divided themselves into various sub-clades within their respective clades, based on the presence of unique co-existing mutations. India was dominated by A2a clade (55.60%) followed by A3 (37.38%) and B (7%), but exhibited heterogeneous distribution among various geographical regions. The A2a clade mostly predominated in East India, Western India and Central India, whereas A3 clade prevailed in South and North India. In conclusion, this study highlights the divergent evolution of SARS-CoV-2 strains and co-circulation of multiple clades in India. Monitoring of the emerging mutations would pave ways for vaccine formulation and designing of antiviral drugs.

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