RESUMO
We have previously reported an HIV-1 mutant designated NL-Y226tac that expresses Vif at an ultra-low level, being replication-defective in high-APOBEC3G cells, such as H9. It carries a synonymous mutation within the splicing SA1 site relative to its parental clone. In order to determine whether a certain mutant(s) emerges during multi-infection cycles, we maintained H9 cells infected with a relatively low or high input of NL-Y226tac for extended time periods. Unexpectedly, we reproducibly identified a g5061a mutation in the SD2b site in the two independent long-term culture experiments that partially increases Vif expression and replication ability. Importantly, the adaptive mutation g5061a was demonstrated to enhance vif mRNA production by activation of the SA1 site mediated through increasing usage of a rarely used SD2b site. In the long-term culture initiated by a high virus input, we additionally found a Y226Fttc mutation at the original Y226tac site in SA1 that fully restores Vif expression and replication ability. As expected, the adaptive mutation Y226Fttc enhances vif mRNA production through increasing the splicing site usage of SA1. Our results here revealed the importance of the SD2b nucleotide sequence in producing vif mRNA involved in the HIV-1 adaptation and of mutual antagonism between Vif and APOBEC3 proteins in HIV-1 adaptation/evolution and survival.
Assuntos
HIV-1 , RNA Mensageiro/genética , HIV-1/fisiologia , Linhagem Celular , Produtos do Gene vif do Vírus da Imunodeficiência Humana/genética , Produtos do Gene vif do Vírus da Imunodeficiência Humana/metabolismo , Replicação Viral/genética , Citidina Desaminase/genética , MutaçãoRESUMO
HIV prevalence among transgender women (TW) in Ho Chi Minh City is estimated at 18 %. However, no evidence-based programs or surveillance data exist in Vietnam specific to HIV testing uptake. We examined prevalence and correlates of past-year HIV testing among TW (n = 204) recruited in 2015 via snowball sampling. 59.3 % reported HIV testing in the previous year. In adjusted models, factors positively associated with HIV testing included consistent condom use during sex work with male clients; STI testing in past year; sex with casual partners in the past month; and experiences of police harassment. Factors negatively associated with recent HIV testing included daily/weekly alcohol use and post-traumatic stress symptoms. This study found significant associations between greater safety in sexual behaviors and higher rates of HIV testing. Targeted and specific services are needed for TW in Vietnam in order to address sexual risk behaviors and provide appropriate access to regular HIV testing.