Analysis of sequence diversity and selection pressure in HIV-1 clade C gp41 from India
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ORIGINAL ARTICLE
Analysis of sequence diversity and selection pressure in HIV-1 clade C gp41 from India Jyoti Sutar1 • Varsha Padwal1 • Vidya Nagar2 • Priya Patil2 • Vainav Patel1 Atmaram Bandivdekar1
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Received: 16 January 2020 / Accepted: 28 April 2020 Ó Indian Virological Society 2020
Abstract Evaluation of viral diversity is critical for the rational design of treatment modalities against Human immunodeficiency virus (HIV). Predominated by HIV-1 clade C (HIV-1C), the epidemic in India represents the third largest population infected with HIV-1 globally. Glycoprotein 41 (gp41) is critical for viral replication and is a target for the design of therapeutic strategies. However, documentation of viral diversity of gp41 gene in infected individuals from India remains limited. Present study employed high throughput sequencing to examine variation in gp41 amplicons generated from blood derived viruses in 24 HIV-1C infected individuals from Mumbai, India. Sequence diversity profiles were documented in different functional domains of gp41. Furthermore, through a metaanalysis approach, all reported gp41 sequences from India (N = 70) were compared with those from South Africa (N = 126), country with the largest HIV epidemic globally, also predominated by HIV-1C. A total of 44 positions displayed statistically significant differential (p \ 0.05) Shannon entropy in the two regions. This comparison also identified 11 codon sites undergoing distinct selection, 8 of
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13337-020-00595-x) contains supplementary material, which is available to authorized users. & Vainav Patel [email protected] & Atmaram Bandivdekar [email protected] 1
Department of Biochemistry, National Institute for Research in Reproductive Health (NIRRH), Indian Council of Medical Research (ICMR), Parel, Mumbai, India
2
Department of Medicine, Grant Government Medical College, Byculla, Mumbai, India
which remained differentially selected in an extended comparison of data from Asia (N = 137) and Africa(N = 383). Assessment of correlated mutation networks associated with differentially selected residues revealed common as well as distinct interaction networks. Furthermore, codon usage analysis revealed 17 differentially selected codons (Mann–Whitney test, p \ 0.001) in Asia and Africa. Dissimilar trends in GC content across codon positions were also observed. In depth understanding of these divergent evolutionary signatures through extended analysis with larger data-sets would assist development of effective interventions being considered for HIV-1C. Keywords HIV-1C India gp41 Evolution Viral variation Codon usage
Introduction Preventing HIV infection as an interventionist strategy has remained elusive due to continual immune escape by the virus facilitated through antigenic variability which the host immune system is unable to surmount. Factors underlying this variability are poor proofreading activity of the reverse transcriptase enzyme, base subst
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