Characterization of HIV-1 integrase N-terminal mutant viruses.
During infection, human immunodeficiency virus type 1 integrase engages a number of molecules and mechanisms, both of viral and cellular origin. In one of such instances, integrase is thought to be degraded by the N-end rule proteasome pathway a process that targets the N-terminal residue of its substrates. Here we describe the properties of HIV-1 viruses in which the first amino acid residue of integrase has been substituted to render it resistant to the N-end rule pathway. As result of this exchange, we observe a set of class I and class II defects that result in a large decrease of viral replication efficiency. Specifically, reverse transcription and integration are the steps that appear to be affected. We propose that the severe deficiency of these mutants exert a strong selective pressure that leads to the near total conservation of the N-terminal residue of integrase in HIV-1, HIV-2 and SIV.
Lloyd
Aliza G
AG
The Aaron Diamond AIDS Research Center 455 First Avenue, New York, NY 10016, USA.
Ng
Yen Shing
YS
Muesing
Mark A
MA
Simon
Viviana
V
Mulder
Lubbertus C F
LC
D019943:Amino Acid Substitution; D002478:Cells, Cultured; D015658:HIV Infections / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear; D009154:Mutation; D010649:Phenylalanine / Q000235:genetics; D016662:Virus Integration; D014779:Virus Replication / Q000235:genetics
D010649:Phenylalanine; D019427:HIV Integrase