Virulence and Replicative Fitness of HIV-1 Transmitted/Founder (T/F) Viruses Harbouring Drug Resistance-Associated Mutation

Sonawane, Aanand and Selvam, Deepak and Yue, Ling and Manohar Nesakumar, Sathiaseelan and Vivekanandan, Sandhya and Ashok kumar, Manickam and Hunter, Eric and Hanna, Luke Elizabeth (2024) Virulence and Replicative Fitness of HIV-1 Transmitted/Founder (T/F) Viruses Harbouring Drug Resistance-Associated Mutation. Virulence and Replicative Fitness of HIV-1 Transmitted/Founder (T/F) Viruses Harbouring Drug Resistance-Associated Mutation, 16 (12). pp. 1-18.

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Abstract

The biological characteristics of early transmitted/founder (T/F) variants are crucial factors for viral transmission and constitute key determinants for the development of better therapeutics and vaccine strategies. The present study aimed to generate T/F viruses and to characterize their biological properties. For this purpose, we constructed 18 full-length infectious molecular clones (IMCs) of HIV from recently infected infants. All the clones were characterized genotypically through whole genome sequencing and phenotypically for infectivity, replication kinetics, co-receptor usage, as well as their susceptibility to neutralizing antibodies and entry inhibitors using standard virological assays. Genotypic analysis revealed that all the T/F clones were of non-recombinant subtype C, but some of them harboured the Y181C drug resistance mutation associated with resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of antiretroviral drugs. In vitro studies showed that while all the IMCs were capable of replicating in PBMCs and utilized the CCR5 co�receptor for cellular entry, the drug-resistant variants had significantly lower replicative capacity and per particle infectivity than the drug-sensitive viruses. Both exhibited similar sensitivities to a standard panel of broadly neutralizing monoclonal antibodies and viral entry inhibitors. These findings suggest that despite their diminished replicative fitness, the drug-resistant T/F variants retain transmission fitness and remain susceptible to neutralizing antibody-based interventions and viral entry inhibitors

Affiliation:	ICMR-National Institute for Research in Tubercuosis
Item Type:	Article
URI:	http://eprints.nirt.res.in/id/eprint/2070

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