Generation and mucosal transmissibility of emtricitabine- and tenofovir-resistant SHIV162P3 mutants in macaques

Mian er Cong, Ae S. Youngpairoj, Wutyi Aung, Sunita Sharma, James Mitchell, Charles Dobard, Walid Heneine, J. Gerardo Garcia-Lerma

Research output: Contribution to journalArticle

Abstract

Transmission of drug-resistant HIV has been widely documented. We generated tenofovir (TFV)- and emtricitabine (FTC)-resistant SHIV162P3 mutants that can be used to investigate the transmission efficiency of drug-resistant viruses and their impact on the efficacy of pre-exposure prophylaxis. Both SHIV162p3 M184V and SHIV162p3 K65R replicated in vitro at high titers. Drug resistance profiles were similar to those seen in HIV. Virus infectivity to virion particle ratios were 4- and 10-fold lower in SHIV162p3 M184V and SHIV162p3 K65R, compared to a concurrently generated WT SHIV162p3, respectively. Mucosal transmissibility studies using a repeat low-dose macaque model of rectal and vaginal transmission showed that both mutants were able to efficiently infect macaques only after the dose was increased to adjust for fitness reductions due to K65R and M184V. Our results in limited number of macaques suggest that the reduction in fitness due to M184V and K65R decreases virus transmissibility, and identify in vitro infectivity parameters that associate with mucosal transmissibility.

Original languageEnglish (US)
Pages (from-to)435-440
Number of pages6
JournalVirology
Volume412
Issue number2
DOIs
StatePublished - Apr 10 2011

Keywords

  • HIV-1 drug resistance
  • Mucosal transmissibility
  • Pre-exposure prophylaxis

ASJC Scopus subject areas

  • Virology

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  • Cite this

    Cong, M. E., Youngpairoj, A. S., Aung, W., Sharma, S., Mitchell, J., Dobard, C., Heneine, W., & Garcia-Lerma, J. G. (2011). Generation and mucosal transmissibility of emtricitabine- and tenofovir-resistant SHIV162P3 mutants in macaques. Virology, 412(2), 435-440. https://doi.org/10.1016/j.virol.2011.01.038