Bukrinskaya A, Brichacek B, Stevenson M; Keystone Symposia on Molecular and Cellular Biology: 1998 HIV Pathogenesis and Treatment.
Keyst Symp Mol Cell Biol Keyst Symp Mol Cell Biol. 1998 Mar 13-19; 62 (abstract no. 3013).
Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester, MA.
Productive infection of the host cell by HIV-1 requires that the virus gains access to the nucleus where viral DNA integrates with host cell DNA. Following host cell infection, viral nucleic acids are synthesized and translocated to the host cell nucleus as a high molecular weight reverse transcription complex. This complex exhibits nucleophilic properties which promotes its translocation into the nucleus via the nuclear pore complex. However, processes which mediate unidirectional transport of the reverse transcription complex from the point of virus entry to the nuclear envelope are not known. We present evidence that the presence of an intact cytoskeleton is necessary for efficient infection of the host cell by HIV-1. Viral reverse transcription complexes rapidly associated with the cytoskeleton upon infection of the cell. Binding of phosphorylated gag MA, which is an integral component of the reverse transcription complex with actin mediated the interaction between the complex and the host cell cytoskeleton. Disruption of the actin network before, but not several hours after virus infection markedly inhibited virus infection. The block to virus infection was due both to a defect in a late stage in reverse transcription and to inefficient entry of the reverse transcription complex into the host cell nucleus. These results suggest that the cytoskeleton provides a framework for unidirectional transport of the viral reverse transcription complex and additionally that engagement of the cytoskeleton is important for the reverse transcription function of this complex.
Publication Types:
Keywords:
- Actins
- Cell Nucleus
- Cytoskeleton
- DNA, Viral
- HIV-1
- reverse transcriptase, Human immunodeficiency virus 1
Other ID:
UI: 102236778
From Meeting Abstracts