Gag-Pol bearing a reverse transcriptase drug-resistant mutation influences viral genomic RNA incorporation into human immunodeficiency virus type 1 particles.
The unspliced human immunodeficiency virus type 1 (HIV-1) RNA is both the messenger for Gag and Gag-Pol and the viral genomic RNA (vRNA) that is packaged into the virion. Although Gag alone is sufficient for the incorporation of vRNA into virus particles, Gag-Pol molecules play an important role in vRNA dimerization and virion maturation. Here, a cis model for vRNA packaging was demonstrated, in which nascent Gag-Pol molecules were preferentially co-encapsulated with their cognate RNA used as the template. Genome-incorporation frequencies were evaluated for two distinct HIV-1 proviral clones differing in their ability to respond to nevirapine (NVP) treatment in one round of infection. It was shown that, under NVP selection, there was a twofold-higher incorporation of vRNAs and integration of provirus genome carrying NVP resistance when compared with the wild-type counterpart. Although cis incorporation has been already demonstrated for Gag, the novelty of these findings is that newly acquired resistant mutations in Gag-Pol will select their specific genomic RNA during virus replication, thus rapidly increasing the chance of the emergence of resistant viruses during the course of anti-retroviral treatment.
Aguiar
Renato S
RS
Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS Bloco A2 sala 121, Cidade Universitária, Ilha do Fundão, 2194421944-970 Rio de Janeiro, Brazil.
Pereira
Helena S
HS
Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS Bloco A2 sala 121, Cidade Universitária, Ilha do Fundão, 2194421944-970 Rio de Janeiro, Brazil.
Costa
Luciana J
LJ
Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS Bloco A2 sala 121, Cidade Universitária, Ilha do Fundão, 2194421944-970 Rio de Janeiro, Brazil.
Brindeiro
Rodrigo M
RM
Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS Bloco A2 sala 121, Cidade Universitária, Ilha do Fundão, 2194421944-970 Rio de Janeiro, Brazil.
Tanuri
Amilcar
A
Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS Bloco A2 sala 121, Cidade Universitária, Ilha do Fundão, 2194421944-970 Rio de Janeiro, Brazil.
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D015750:Genes, gag; D015751:Genes, pol; D016679:Genome, Viral; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D019829:Nevirapine / Q000494:pharmacology; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral / Q000378:metabolism*; D019065:Virus Assembly; D014779:Virus Replication
D004279:DNA, Viral; D012367:RNA, Viral; D019829:Nevirapine; D054303:HIV Reverse Transcriptase