Analysis of pol Gene Heterogeneity, Viral Quasispecies, and Drug Resistance in Individuals Infected with Group O Strains of Human Immunodeficiency Virus Type 1
AUTOR(ES)
Quiñones-Mateu, Miguel E.
FONTE
American Society for Microbiology
RESUMO
Nucleotide sequences of the reverse transcriptase (RT) coding region have been compared in four new human immunodeficiency virus type 1 (HIV-1) group O isolates. Phylogenetic analysis of this pol region highlights a cluster of these four HIV-1 group O sequences with seven other group O isolates (5% intracluster nucleotide sequence diversity) similar to clusters classified as subtypes in HIV-1 group M (an average of 4.9% intrasubtype sequence diversity). Based on these analyses, this group O cluster has been designated subtype A-O. A longitudinal study of a heterosexual couple infected with group O (ESP1 and ESP2) allowed a detailed analysis of RT sequences (amino acids 28 to 219). Directed evolution and a slightly higher mutation frequency was observed in the RT sequences of patient ESP2, treated with antiretroviral drugs, than that from the untreated patient ESP1. Antiretroviral treatment also selected for specific substitutions, M184V and T215Y in the RT coding region, conferring resistance to 3′-dideoxy-3′-thiacytidine and zidovudine, respectively. A Gly98 to Glu RT substitution identified in the treated patient suggests a possible reversion of a nonnucleoside RT inhibitor-resistant phenotype. Using RT clones from this longitudinal study, both heteroduplex tracking assay and cloning-sequencing techniques were employed for an extensive genetic analysis of pol gene quasispecies. Amino acid substitutions (i.e., Phe-77 to Leu, Lys-101 to Glu, and Val-106 to Iso) associated with antiretroviral resistance were identified in RT clones from HIV-1 group O-infected patients not subjected to drug therapy or treated with unrelated drugs. Finally, phylogenetic relationships between RT clones of the treated ESP2 patient and those of the untreated ESP1 patient show how drug pressure can direct evolution of viral pol gene quasispecies independently of direct drug-resistant substitutions.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=110317Documentos Relacionados
- Pol gene quasispecies of human immunodeficiency virus: mutations associated with drug resistance in virus from patients undergoing no drug therapy.
- Antibodies to CD4 in individuals infected with human immunodeficiency virus type 1.
- Accumulation of defective viral genomes in peripheral blood mononuclear cells of human immunodeficiency virus type 1-infected individuals.
- High frequency of isolation of defective human immunodeficiency virus type 1 and heterogeneity of viral gene expression in clones of infected U-937 cells.
- Variability and Immunogenicity of Human Immunodeficiency Virus Type 1 p24 Gene Quasispecies