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Journal of Virology, April 2000, p. 3548-3554, Vol. 74, No. 8
0022-538X/00/$04.00+0

Genetic Evidence for an Interaction between Human Immunodeficiency Virus Type 1 Matrix and alpha -Helix 2 of the gp41 Cytoplasmic Tail

Tsutomu Murakami and Eric O. Freed*

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460

Received 14 December 1999/Accepted 26 January 2000

The incorporation of envelope (Env) glycoproteins into virions is an essential step in the retroviral replication cycle. Lentiviruses, including human immunodeficiency virus type 1 (HIV-1), encode Env glycoproteins with unusually long cytoplasmic tails, the functions of which have not been fully elucidated. In this study, we examine the effects on virus replication of a number of mutations in a helical motif (alpha -helix 2) located near the center of the HIV-1 gp41 cytoplasmic tail. We find that, in T-cell lines, small deletions in this domain disrupt the incorporation of Env glycoproteins into virions and markedly impair virus infectivity. Through the analysis of viral revertants, we demonstrate that a single amino acid change (34VI) in the matrix domain of Gag reverses the Env incorporation and infectivity defect imposed by a small deletion near the C terminus of alpha -helix 2. These results provide genetic evidence, in the context of infected T cells, for an interaction between HIV-1 matrix and the gp41 cytoplasmic tail and identify domains of both proteins involved in this putative interaction.

* Corresponding author. Mailing address: Bldg. 4, Rm. 307, NIAID, NIH, Bethesda, MD 20892-0640. Phone: (301) 402-3215. Fax: (301) 402-0226. E-mail: EFreed{at}nih.gov.

Journal of Virology, April 2000, p. 3548-3554, Vol. 74, No. 8
0022-538X/00/$04.00+0


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