Sexual transmission of HIV-1 isolate showing G-->A hypermutation.
Retroviral genomes with a high frequency of G-->A mutations are thought to originate during reverse transcription (RT). Here we present a case report of an AIDS patient infected with a subtype F variant where extensive G-->A hypermutation (G-->A Hypm) sequences were found in the protease gene. This patient was failing HAART at the time the hypermutation was found. These sequences were basically encountered in the proviral compartment on two occasions and were persistently absent in the plasma viral population. The patient's viral genotype showed several mutations related to antiretroviral drug resistance in RT (T69N, M184V, T215F, K219Q) and protease (M36I, G48V, I54V, T63L, V82A) genes. The drug regimen was changed and the viral load dropped 0.9 Logs and CD4 count increased by 200 cells/ml. The hypermutation was not found any more in a 1-year follow up. The patient's wife was infected with a similar virus strain and G-->A Hypm sequences were also detected in the RT gene. This is the first report of sexual transmitted G-->A Hypermutation in HIV-1 and suggest that this phenomenon can be genetically coded by the viral RT molecule.
Caride
Elena
E
Genetics Department, Laboratory of Molecular Virology, Universidade Federal do Rio de Janeiro, UFRJ, Bloco A, sala 121, 2o andar, 21944-970, Rio de Janeiro, Brazil.
Brindeiro
Rodrigo M
RM
Kallas
Esper G
EG
de Sá
Carlos Alberto M
CA
Eyer-Silva
Walter A
WA
Machado
Elizabeth
E
Tanuri
Amilcar
A
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000635:transmission / Q000821:virology*; D000328:Adult; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D016415:Sequence Alignment
D019380:Anti-HIV Agents; D054303:HIV Reverse Transcriptase; D016333:HIV Protease