HIV Infection: Shaping the Complex, Dynamic, and Interconnected Network of the Cytoskeleton.
Date
2023Abstract
HIV-1 has evolved a plethora of strategies to overcome the cytoskeletal barrier (i.e., actin
and intermediate filaments (AFs and IFs) and microtubules (MTs)) to achieve the viral cycle. HIV-1
modifies cytoskeletal organization and dynamics by acting on associated adaptors and molecular
motors to productively fuse, enter, and infect cells and then traffic to the cell surface, where virions
assemble and are released to spread infection. The HIV-1 envelope (Env) initiates the cycle by binding
to and signaling through its main cell surface receptors (CD4/CCR5/CXCR4) to shape the cytoskeleton for fusion pore formation, which permits viral core entry. Then, the HIV-1 capsid is transported
to the nucleus associated with cytoskeleton tracks under the control of specific adaptors/molecular
motors, as well as HIV-1 accessory proteins. Furthermore, HIV-1 drives the late stages of the viral
cycle by regulating cytoskeleton dynamics to assure viral Pr55Gag expression and transport to the cell
surface, where it assembles and buds to mature infectious virions. In this review, we therefore analyze
how HIV-1 generates a cell-permissive state to infection by regulating the cytoskeleton and associated
factors. Likewise, we discuss the relevance of this knowledge to understand HIV-1 infection and
pathogenesis in patients and to develop therapeutic strategies to battle HIV-1.