Role of Microtubules and Microtubule-Associated Proteins in HIV-1 Infection

Abstract

Recent studies show that human immunodeficiency virus type 1 (HIV-1) can utilize microtubules and their associated proteins to complete key postfusion steps during infection. These include associating with both dynein and kinesin motors, as well as proteins, which enhance infection by altering microtubule dynamics during infection. In this article, we will discuss findings on how dynein and kinesin motors, as well as other microtubule-associated proteins, influence HIV-1 trafficking, viral core uncoating, and nuclear import of the viral ribonucleoprotein (RNP).

Keywords: BICD2; EB1; FEZ1; HIV-1; dynein; kinesin-1; microtubules.

FIG 1

Model of HIV-1 postfusion trafficking. Following envelope-mediated fusion, the viral capsid core is released into the cytoplasm. (A) Normal scenario of HIV-1 retrograde trafficking toward the nucleus. Virus infection triggers EB1, DRF kif4, and MAP1 to stabilize MT to promote HIV-1 infection. Once in the cytoplasm of the target cell, the viral core recruits dynein motor adaptor BICD2 and kinesin-1 motor adaptor Fez1. BICD2 recruits dynein on to the viral capsid and mediates retrograde movement toward the nucleus. (B) Scenario of HIV-1 bidirectional transport. (1) When the viral capsid encounters a roadblock, such as organelle trafficking in the opposing direction along the same MT, to overcome this obstacle, the capsid undergoes anterograde movement by recruiting kinesin-1 through Fez1 adaptor. (2) Once the viral capsid overcomes the obstacle and reaches a neighboring MT, kinesin-1 motility is switched off by Fez1 phosphorylation, thus enabling BICD2-dynein to continue the retrograde movement toward the nucleus.