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

被引：14

作者：

Cong, Mian-er ^{[1
]}

Youngpairoj, Ae S. ^{[1
]}

Aung, Wutyi ^{[1
]}

Sharma, Sunita ^{[1
]}

Mitchell, James ^{[1
]}

Dobard, Charles ^{[1
]}

Heneine, Walid ^{[1
]}

Garcia-Lerma, J. Gerardo ^{[1
]}

机构：

[1] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Natl Ctr HIV Hepatitis STD & TB Prevent, Branch Lab, Atlanta, GA 30329 USA

来源：

VIROLOGY | 2011年 / 412卷 / 02期

关键词：

HIV-1 drug resistance; Mucosal transmissibility; Pre-exposure prophylaxis; HUMAN-IMMUNODEFICIENCY-VIRUS; HIV PRECLINICAL INTERVENTIONS; REVERSE-TRANSCRIPTASE; RHESUS MACAQUES; DRUG-RESISTANCE; ANTIRETROVIRAL THERAPY; NONHUMAN-PRIMATES; TYPE-1; FITNESS; MUTATIONS;

D O I：

10.1016/j.virol.2011.01.038

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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. Published by Elsevier Inc.

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页码：435 / 440

页数：6

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