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Capsid-host interactions for HIV-1 ingress.

Sooin Jang1,2, Alan N Engelman1,2

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The HIV-1 capsid

Keywords:
CPSF6FG domainHIVNUP153capsidlenacapavirliquid-liquid phase separationmixed-charge domainnuclear importprion-like domainspeckle-associated domaintrafficking

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Area of Science:

  • Virology
  • Structural Biology
  • Molecular Biology

Background:

  • The human immunodeficiency virus type 1 (HIV-1) capsid protein forms a protective shell around viral genetic material and essential enzymes.
  • Understanding HIV-1 capsid interactions with host factors is crucial for viral entry and replication.
  • The precise timing and location of HIV-1 capsid uncoating during the infection process remain subjects of debate.

Purpose of the Study:

  • To review the complex interactions between the HIV-1 capsid and host factors during viral entry and nuclear import.
  • To discuss current research questions regarding HIV-1 capsid uncoating dynamics.
  • To highlight the clinical relevance of targeting capsid-host interactions.

Main Methods:

  • Review of existing literature on HIV-1 capsid structure, function, and host interactions.
  • Analysis of recent findings on capsid uncoating and nuclear pore complex traversal.
  • Discussion of the role of specific host factors, such as CPSF6, and their binding motifs (e.g., FG motifs, PrLDs).

Main Results:

  • Recent evidence suggests the HIV-1 capsid may remain largely intact during nuclear import, with potential structural remodeling for NPC passage.
  • Host factors, including those with prion-like domains, bind to the capsid exterior, facilitating productive infection.
  • Completion of reverse transcription in the nucleus may contribute to capsid disassembly.

Conclusions:

  • HIV-1 capsid-host interactions are critical for viral ingress and subsequent replication.
  • Targeting these interactions, as exemplified by the drug lenacapavir, offers a promising therapeutic strategy.
  • Further research is needed to fully elucidate the mechanisms and timing of HIV-1 capsid uncoating.