Bukrinsky M, Haggerty S, Stevenson M, Shapiro I, Goldfarb D; International Conference on AIDS.

Int Conf AIDS. 1993 Jun 6-11; 9: 18 (abstract no. WS-A02-2).

Picower Institute for Medical Research, Manhasset, New York.

Integration of the retroviral genome with cellular DNA and establishment of the provirus is an essential step in retrovirus replication. Integration requires targeting of the viral preintegration complex to host cell DNA and is, therefore, dependent on transport of this complex to the nucleus of the host cell. Analysis of the HIV-1 preintegration complex transport revealed that this process is independent of cell division and requires ATP, features indicative of active transport. Analysis of the preintegration complex revealed HIV-1 matrix antigen (MA) p17 as a component. Our studies indicate that by virtue of a nuclear localization signal (NLS) at the N terminus of MA, this protein is important for nuclear import of the HIV-1 preintegration complex. Mutations within this NLS restrict nuclear import of HIV-1 DNA following virus infection of non-dividing, but not of actively proliferating cells. Therefore, HIV-1 appears to use different strategies for infection of different types of cells: one strategy similar to the one used by oncogenic retroviruses relies on nuclear membrane dissolution during mitosis, and another one common to the subgroup of lentiviruses exploits active transport for entering the nuclear compartment. The presence of an active transport pathway for nuclear import of HIV-1 preintegration complexes explains the ability of HIV-1 to infect non-dividing cells (i.e. macrophages) and suggests a new target for antiviral therapy aimed at the early steps of viral replication.

Publication Types:

• Meeting Abstracts

Keywords:

• Acquired Immunodeficiency Syndrome
• Active Transport, Cell Nucleus
• Biological Transport
• Cell Division
• Cell Nucleus
• HIV Infections
• HIV-1
• Nuclear Localization Signals
• Proviruses
• Retroviridae Infections
• genetics
• reverse transcriptase, Human immunodeficiency virus 1

Other ID:

• 93333708

UI: 102203082

From Meeting Abstracts