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In Old World primates, TRIM5-alpha confers a potent block to human immunodeficiency virus type 1 (HIV-1) infection that acts after virus entry into cells. Cyclophilin A (CypA) binding to viral capsid protects HIV-1 from a similar activity in human cells. Among New World primates, only owl monkeys exhibit post-entry restriction of HIV-1 (ref. 1).(More)
Little is known about host factors necessary for retroviral virion assembly or uncoating. We have previously shown that the principal structural protein of the human immunodeficiency virus HIV-1, the Gag polyprotein, binds the cyclophilin peptidyl-prolyl isomerases; cyclophilins catalyse a rate-limiting step in protein folding and protect cells from heat(More)
TRIM5 is a RING domain-E3 ubiquitin ligase that restricts infection by human immunodeficiency virus (HIV)-1 and other retroviruses immediately following virus invasion of the target cell cytoplasm. Antiviral potency correlates with TRIM5 avidity for the retrovirion capsid lattice and several reports indicate that TRIM5 has a role in signal transduction, but(More)
Host cells impose a broad range of obstacles to the replication of retroviruses. Tetherin (also known as CD317, BST-2 or HM1.24) impedes viral release by retaining newly budded HIV-1 virions on the surface of cells. HIV-1 Vpu efficiently counteracts this restriction. Here, we show that HIV-1 Vpu induces the depletion of tetherin from cells. We demonstrate(More)
Many mammalian species express restriction factors that confer host resistance to retroviral infection. Here we show that HIV-1 sensitivity to restriction factors is modulated by cyclophilin A (CypA), a host cell protein that binds the HIV-1 capsid protein (CA). In certain nonhuman primate cells, the CA-CypA interaction is essential for restriction: HIV-1(More)
The retinoblastoma tumor suppressor protein (RB) binds several cellular proteins involved in cell cycle progression. Using the yeast two-hybrid system, we found that RB bound specifically to the protein BRG1. BRG1 shares extensive sequence similarity to Drosophila brahma, an activator of homeotic gene expression, and the yeast transcriptional activator(More)
Retroviral Gag protein is capable of directing the assembly of virion particles independent of other retroviral elements and plays an important role early in the infection of a cell. Using the GAL4 two hybrid system, we screened a cDNA expression library and identified two host proteins, cyclophillins (CyPs) A and B, which interact specifically with the(More)
Cyclophilin A (CyPA) is incorporated into human immunodeficiency virus type 1 (HIV-1) virions via contact with the Gag polyprotein. Genetic or pharmacologic disruption of CyPA incorporation causes a quantitative reduction in virion infectivity with no discernible effects on virion assembly or on endogenous reverse transcriptase activity. Instead, the(More)
Despite intensive investigation the mechanism by which HIV-1 reaches the host cell nucleus is unknown. TNPO3, a karyopherin mediating nuclear entry of SR-proteins, was shown to be required for HIV-1 infectivity. Some investigators have reported that TNPO3 promotes HIV-1 nuclear import, as would be expected for a karyopherin. Yet, an equal number of(More)
Viruses are obligate intracellular parasites and therefore their replication completely depends on host cell factors. In case of the hepatitis C virus (HCV), a positive-strand RNA virus that in the majority of infections establishes persistence, cyclophilins are considered to play an important role in RNA replication. Subsequent to the observation that(More)