AEGiS-14IAC: Reversion of HIV-1 with mutations in the tryptophan-rich region of gp41.

14th International AIDS Conference


Barcelona, Spain - July 7-12, 2002

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Reversion of HIV-1 with mutations in the tryptophan-rich region of gp41.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. TuOrA1138)

Yu Q, Hunter E
University of Alabama at Birmingham, Birmingham, AL, United States

BACKGROUND: The membrane-proximal region in the ectodomain of HIV gp41 contains five highly conserved tryptophans that are biologically important for the envelope glycoprotein (Env) incorporation and virus infectivity. The role of this gp41 tryptophan-rich region in the structure and function of Env remains unclear. In this study, we further analyzed two HIV-1 mutants which contain multiple alanine substitutions in the gp41 membrane proximal region. These viruses have been demonstrated previously to have low infectivity and Env incorporation.

METHODS: NL4-W(1,3,4)A and NL4-W(2-5)A viruses generated by transfection were used to infect Sup T1 cells. Virus growth and the infectivity of the released viruses were determined.

RESULTS: Although the mutant viruses were able to spread through the cultures, the infectivity of the early-released mutant viruses remained at least one log lower than the wild type virus. The infectivity of the viruses gradually improved and reached wild type levels by day 70 post-infection. Sequence analysis of the viruses at 70d post-infection revealed that the viruses maintained the alanine substitutions in gp41, indicating that second-site mutations are responsible for the reversion of virus infectivity. Preliminary analysis of the entire gp41 region of W(1,3,4)A virus at 70d post-infection identified two consistent amino acid substitutions. Studies are ongoing to determine the role of these mutations in the reversion event. To address the possibility that compensating mutations occurred in the viral matrix protein, this region of the revertant viruses was analyzed but no changes were detected.

CONCLUSIONS: Taken together, our studies indicate that mutations in the highly conserved membrane-proximal tryptophans in gp41 can be overcome by second-site mutations in the virus. Ongoing study to further delineate these compensating mutations will provide insight on the structure and function of HIV-1 Env.

Keywords: AEGIS, HIV-1, Mutation, Tryptophan, HIV Infections, Amino Acid Substitution, Viral Matrix Proteins, geneticsKWDaegis,hiv-1,mutation,tryptophan,hivinfections,aminoacidsubstitution,viralmatrixproteins,genetics

020707
TuOrA1138

Copyright © 2002 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.