2nd National Conference Human Retroviruses and Related Infections Washington, DC - January 29 - February 2, 1995

Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 29)

Di Marzio P¹, Choe S¹, Connor RI¹, Knoblauch R², Ebright M², Isakoff S², Landau NR^1,2*
1Aaron Diamond AIDS Research Center, 455 First Avenue, New York, N.Y. 10016; ²New York University Medical School, New York, N.Y. 10016

Vpr is a highly conserved gene of HIV/SIV that is important in AIDS pathogenesis but appears to play no role in infection of transformed cell-lines. Unlike the other HIV-1 regulatory gene products it is abundant in virions. A recent report suggested that Vpr facilitates import of the HIV-1 preintegration complex into the nucleus of non-dividing cells following entry of the virus into the cytoplasm. By studying the incorporation of mutant Vpr molecules into the HIV-1 virions, we have shown that an amino-terminal region of Vpr (amino acids 17-34) which is predicted to form an alpha helix is important for incorporation of Vpr into the virion. Immunofluorescence studies show that this region also plays a role in nuclear localization of the protein. In addition, we have investigated the ability of Vpr to act as a carrier to allow incorporation of large proteins into virions. These studies showed that an intermediate size protein (55 k-Da) but not a large protein (110 k-Da) were incorporated into virions when fused to either the N- or C- terminus of Vpr. Functional studies using novel luciferase and alkaline phosphatase HIV-1 reporter vectors showed that Vpr significantly increases the ability of HIV-1 to infect monocytes but does not play a role in resting or activated PBMC. These experiments also showed, in agreement with a recent report, that Vpr appears to overlap in function with the matrix nuclear localization sequence in allowing infection of nondividing cells. In monocytes, Vpr appears to have an additional role subsequent to nuclear import.

Keywords: Base Sequence, Cell Nucleus, Cytoplasm, Genes, vpr, HIV, HIV Protease, HIV-1, Monocytes, Virion, genetics

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1995-01-29
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