Dynactin 1 negatively regulates HIV-1 infection by sequestering the host cofactor CLIP170

Shanmugapriya Shanmugapriya, Eveline Santos da Silva, Jackson A. Campbell, Marie Philipe Boisjoli, Mojgan H. Naghavi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Many viruses directly engage and require the dynein–dynactin motor–adaptor complex in order to transport along microtubules (MTs) to the nucleus and initiate infection. HIV type 1 (HIV-1) exploits dynein, the dynein adaptor BICD2, and core dynactin subunits but unlike several other viruses, does not require dynactin-1 (DCTN1). The underlying reason for HIV-1’s variant dynein engagement strategy and independence from DCTN1 remains unknown. Here, we reveal that DCTN1 actually inhibits early HIV-1 infection by interfering with the ability of viral cores to interact with critical host cofactors. Specifically, DCTN1 competes for binding to HIV-1 particles with cytoplasmic linker protein 170 (CLIP170), one of several MT plus-end tracking proteins (+TIPs) that regulate the stability of viral cores after entry into the cell. Outside of its function as a dynactin subunit, DCTN1 also functions as a +TIP that we find sequesters CLIP170 from incoming particles. Deletion of the Zinc knuckle (Zn) domain in CLIP170 that mediates its interactions with several proteins, including DCTN1, increased CLIP170 binding to virus particles but failed to promote infection, further suggesting that DCTN1 blocks a critical proviral function of CLIP170 mediated by its Zn domain. Our findings suggest that the unique manner in which HIV-1 binds and exploits +TIPs to regulate particle stability leaves them vulnerable to the negative effects of DCTN1 on +TIP availability and function, which may in turn have driven HIV-1 to evolve away from DCTN1 in favor of BICD2-based engagement of dynein during early infection.

Original languageEnglish (US)
Article numbere2102884118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number43
StatePublished - Oct 26 2021


  • +TIPs
  • CLIP170
  • Capsid uncoating
  • DCTN1
  • HIV-1

ASJC Scopus subject areas

  • General


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