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Effect of Mutations in the Human Immunodeficiency Virus Type 1 Protease on Cleavage of the gp41 Cytoplasmic Tail

  1. Author:
    Waheed, A. A.
    Ablan, S. D.
    Sowder, R. C.
    Roser, J. D.
    Schaffner, C. P.
    Chertova, E.
    Freed, E. O.

  2. Author Address

    [Waheed, Abdul A.; Ablan, Sherimay D.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Sowder, Raymond C.; Roser, James D.; Chertova, Elena] NCI, AIDS & Canc Virus Program, SAIC, Frederick, MD 21702 USA. [Schaffner, Carl P.] Rutgers State Univ, Waksman Inst, Dept Microbiol & Biochem, New Brunswick, NJ 08903 USA.;Waheed, AA, NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Bldg 535,Rm 108, Frederick, MD 21702 USA.;awaheed@ncifcrf.gov
    1. Year: 2010
    2. Date: Mar
  2. Journal: Journal of Virology
    1. 84
    2. 6
    3. Pages: 3121-3126
  4. Type of Article: Article
  5. ISSN: 0022-538X
  1. Abstract:

    We previously reported that human immunodeficiency virus type 1 (HIV-1) develops resistance to the cholesterol-binding compound amphotericin B methyl ester (AME) by acquiring mutations (P203L and S205L) in the cytoplasmic tail of the transmembrane envelope glycoprotein gp41 that create cleavage sites for the viral protease (PR). In the present study, we observed that a PR inhibitor-resistant (PIR) HIV-1 mutant is unable to efficiently cleave the gp41 cytoplasmic tail in P203L and S205L virions, resulting in loss of AME resistance. To define the pathway to AME resistance in the context of the PIR PR, we selected for resistance with an HIV-1 isolate expressing the mutant enzyme. We identified a new gp41 mutation, R236L, that results in cleavage of the gp41 tail by the PIR PR. These results highlight the central role of gp41 cleavage as the primary mechanism of AME resistance.

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External Sources

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  2. DOI: 10.1128/jvi.02002-09
  3. View record in Web of Science®
  4. WOS: 000275322300048

Library Notes

  1. Fiscal Year: FY2009-2010
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