3rd Conference on Retroviruses and Opportunistic Infections


Washington, DC - January 28-February 1, 1996


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CHARACTERIZATION OF HIV-1 MATRIX FUNCTION: ANALYSIS OF VIRAL REVERTANTS.

Conf Retroviruses Opportunistic Infect 1996 Jan 28-Feb 1; 3rd:56 (abstract no. 20)

Freed EO, Martin MA
NIAID, NIH, Bethesda, MD.


To characterize functions of HIV-1 matrix (MA) and define domains involved in these functions , we have introduced over 65 single and double amino acid substitutions throughout MA. The effects on a number of aspects of the virus life cycle, including Gag expression and processing , virus particle assembly and production , virus infectivity in a range of celltypes ,an envelope(Env) glycoprotein incorporation into virions, were determined. Several classes of mutations were identified , including those that: i) blocked virus assembly, ii) redirected assembly from the plasma membrane to cytoplasmic compartments, iii) interfered with virus entry, or iv) blocked Env incorporation into virions without affecting virus assembly and release.

During the course of this analysis, viral revertants of all classes of mutations were obtained and characterized. For example, a Val -> Ile change at residue 34 compensated for two position 12 mutations which blocked Env incorporation into virions, and a Gln -> Lys substitution at residue 27 (in the MA highly-basic domain) reversed the phenotype of a position 86 mutation which redirected virus assembly to the cytoplasm. The implications of the mutational analysis and revertant characterization for understanding MA structure/function relationships and delineating the role of MA in the HIV-1 life cycle will be presented.

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Copyright © 1996 - Foundation for Retrovirology and Human Health . Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health.