QUASISPECIES FEATURE IN SARS-CoV-2

Since the identification of the SARS-CoV-2, genus Beta- Coronavirus, in January 2020, the virus quickly spread in less than 3 months to all continents with a susceptible human population of about a 7.9billion, and still in active circulation. In the process, it has accumulated mutations leading to genetic diversity. Regular emergence of variants of concern/significance in different ecology shows genetic heterogeneity in the base population of SARS-CoV-2 that is continuously expanding with the passage of the virus in the vast susceptible human population. Natural selection of mutant occurs frequently in a positive sense (+) single-stranded (ss) RNA virus upon replication in the host.  The Pressure of sub-optimal levels of virus-neutralizing antibodies and also innate immunity influence the process of genetic/ antigenic selection. The fittest of the mutants, that could be more than one, propagate and emerge as variants. The existence of different lineages, clades, and strains, as well as genetic heterogeneity of plaque purified virus population, justifies SARS-CoV-2 as ‘Quasispecies’ that refers to swarms of mutant sequences generated during replication of the viral genome, and all mutant sequences may not lead to virion. Viruses having a quasispecies nature may end up with progressive antigenic changes leading to antigenic plurality that is driven by ecology, and this phenomenon challenges vaccination-based control programs

EVOLUTIONARY ANALYSIS AND DETECTION OF POSITIVE SELECTION OF HEMAGGLUTININ AND NEURAMINIDASE GENES OF H5N1 AVIAN INFLUENZA FROM CHICKEN, DUCK AND GOOSE ACROSS ASIA

Outbreaks of very high pathogenic avian influenza (H5N1) viruses are being reported in poultry in almost all countries including Asia. It has been reported that the spread is very fast and found that this virus is spreading in avian species for several years. In this study, the evidence of positive selection prominent to mutations were analyzed for the Hemagglutinin (HA) and Neuraminidase (NA) nucleotide sequences of H5N1 avian influenza from chicken, duck, and goose across Asia. H5N1 avian influenza viruses are being a severe risk to public health. Detection of positive selection sites in Hemagglutinin (HA) and Neuraminidase (NA) genes will help to trace the evolutionary path of these viruses from different poultry hosts. The positive/ diversifying selection (dN/dS (ω) >1) was found to be showing significant signals in the mutation of HA and NA genes and is evolving rapidly. The cumulative dN/dS (ω) ratio was found ranging from 0.21 to 0.23 in the HA gene and 0.16 to 0.25 in the NA gene of Avian Influenza Virus from chicken, duck, and goose. Furthermore, statistical Bayesian model methods were applied to interpret the genetic diversity of H5N1 strain, the evolutionary rates were ranging from 2.36x10-3 to 5.19x10-3 in the HA gene and 2.28x10-3 to 6.25x10-3 in the NA gene from chicken, duck, and goose respectively, which revealed a rapid evolution in these viruses with respect to their genetic ancestor. Substitution rates and selection pressure in these three different hosts indicate that their dynamics of mutation and replication remain similar among the species studied and are important for evolution

Avian Influenza (H5N1) Virus of Clade 2.3.2 in Domestic Poultry in India

South Asia has experienced regular outbreaks of H5N1 avian influenza virus since its first detection in India and Pakistan in February, 2006. Till 2009, the outbreaks in this region were due to clade 2.2 H5N1 virus. In 2010, Nepal reported the first outbreak of clade 2.3.2 virus in South Asia. In February 2011, two outbreaks of H5N1 virus were reported in the State of Tripura in India. The antigenic and genetic analyses of seven H5N1 viruses isolated during these outbreaks were carried out. Antigenic analysis confirmed 64 to 256-fold reduction in cross reactivity compared with clade 2.2 viruses. The intravenous pathogenicity index of the isolates ranged from 2.80–2.95 indicating high pathogenicity to chickens. Sequencing of all the eight gene-segments of seven H5N1 viruses isolated in these outbreaks was carried out. The predicted amino acid sequence analysis revealed high pathogenicity to chickens and susceptibility to the antivirals, amantadine and oseltamivir. Phylogenetic analyses indicated that these viruses belong to clade 2.3.2.1 and were distinct to the clade 2.3.2.1 viruses isolated in Nepal. Identification of new clade 2.3.2 H5N1 viruses in South Asia is reminiscent of the introduction of clade 2.2 viruses in this region in 2006/7. It is now important to monitor whether the clade 2.3.2.1 is replacing clade 2.2 in this region or co-circulating with it. Continued co-circulation of various subclades of the H5N1 virus which are more adapted to land based poultry in a highly populated region such as South Asia increases the risk of evolution of pandemic H5N1 strains

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Not AvailableSince the identification of the SARS CoV 2 genus Beta Coronavirus in January 2020 the virus quickly spread in less than 3 months to all continents with a susceptible human population of about a 7.9 billion, and still in active circulation. In the process, it has accumulated mutations leading to genetic diversity. Regular emergence of variants of concern/significance in different ecology shows genetic heterogeneity in the base population of SARS CoV 2 that is continuously expanding with the passage of the virus in the vast susceptible human population. Natural selection of mutant occurs frequently in a positive sense single stranded (ss) RNA virus upon replication in the host. The Pressure of sub optimal levels of virus neutralizing antibodies and also innate immunity influence the process of genetic or antigenic selection. The fittest of the mutants, that could be more than one, propagate and emerge as variants. The existence of different lineages, clades, and strains as well as genetic heterogeneity of plaque purified virus population justifies SARS CoV 2 as Quasispecies that refers to swarms of mutant sequences generated during replication of the viral genome and all mutant sequences may not lead to virion. Viruses having a quasispecies nature may end up with progressive antigenic changes leading to antigenic plurality that is driven by ecology and this phenomenon challenges vaccination based control programsNot Availabl

Circulation of H5N1 viruses in South Asia since 2010.

<p>Circulation of H5N1 viruses in South Asia since 2010.</p

Antigenic characterization of Indian clade 2.3.2 H5N1 viruses.

<p>*- reciprocal of antibody titres by hemagglutination inhibition test.</p

Phylogenetic relationships of the coding sequences of hemagglutinin (HA) genes of representative influenza A viruses.

<p>Analysis was based on full length or near full length sequences. The numbers next to the branch nodes indicate bootstrap values/posterior probabilities expressed as percentages from, respectively, 500 bootstrap replicates of a maximum likelihood tree and posterior probabilities from a MrBayes 3.2 analysis (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031844#s3" target="_blank">methods</a>). Not all support valuess are shown due to space constraints. Numbers labeled on the HA tree refer to the WHO H5N1 clade designations (<a href="http://www.who.int/csr/disease/avian_influenza/guidelines/nomenclature/en" target="_blank">http://www.who.int/csr/disease/avian_influenza/guidelines/nomenclature/en</a>). Viruses isolated in this work are in green and other recent Indian, Bangladesh and Bhutan viruses are in red. Scale bar, indicates nucleotide substitutions per site.</p

Circulation of H5N1 viruses in South Asia till 2009.

<p>Circulation of H5N1 viruses in South Asia till 2009.</p

Phylogenetic relationships of polymerase acidic (PA) genes of representative influenza A viruses.

<p>Details are as in the legends to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031844#pone-0031844-g001" target="_blank">Figures 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031844#pone-0031844-g002" target="_blank">2</a>.</p