Mechanism of CypA Inhibition of HIV-1 Infection
Source: Vanderbilt, Leigh MacMillan
The HIV-1 capsid protein (CA) interacts with viral factors that support infection and host factors that restrict it. The host protein cyclophilin A (CypA) binds to CA and enhances the action of host restriction factors that block HIV-1 infection.
Christopher Aiken, Ph.D., and colleagues investigated how CypA potentiates the action of the restriction factor TRIM5alpha in African green monkey cells. They did not find evidence of a role for CypA in promoting binding of TRIM5alpha to the viral capsid or inhibiting reverse transcription of the viral genome.
Instead, the investigators observed a CypA-dependent reduction in the accumulation of nuclear HIV-1 DNA, suggesting that CypA promotes TRIM5alpha inhibition of HIV-1 nuclear import. They reported their findings in the journal PLOS ONE.
The authors propose that CypA uses a common mechanism involving interactions of the virus with nuclear pore components to potentiate restriction of HIV-1 infection by TRIM5alpha and other capsid-targeting inhibitors.
"We want to understand all the details, from when the virus fuses, to the point where it integrates and starts to make new viruses, to the last phase," explained Hope, also a professor of Obstetrics and Gynecology and of the McCormick School of Engineering. "We need to understand what's going on, so we can find the Achilles' heel of the virus and use it as a drug target."
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