Uncovering the evolving arms race between host immunity and HIV-1

Trends Immunol. 2025 Nov;46(11):728-740. doi: 10.1016/j.it.2025.08.004. Epub 2025 Sep 10.

Abstract

Despite an effective combination of antiretroviral therapy, HIV persists as a lifelong infection and global health threat. The human host equips restriction factors and interferon (IFN)-stimulated genes that target every step of the viral life cycle. However, HIV-1 has evolved a coordinated immune evasion strategy using a limited set of accessory proteins with distinct antagonistic functions. This functional division of labor allows HIV-1 to disable key immune pathways and ensure persistence. Here, we explore the molecular interplay between host defenses and HIV-1, organizing antiviral factors by viral life cycle stage. We further reframe viral immune evasion as a strategic division of labor among accessory proteins each adapted to target specific host defenses, offering insights for next-generation therapies.

Keywords: HIV-1; antiviral factors; viral antagonisms.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use
  • Antigens, Differentiation
  • Capsid / drug effects
  • Capsid / immunology
  • Cytokines
  • Genome, Viral
  • HIV Infections* / drug therapy
  • HIV Infections* / immunology
  • HIV Infections* / virology
  • HIV-1* / drug effects
  • HIV-1* / genetics
  • HIV-1* / immunology
  • HIV-1* / physiology
  • Host-Pathogen Interactions* / drug effects
  • Host-Pathogen Interactions* / genetics
  • Host-Pathogen Interactions* / immunology
  • Humans
  • Immune Evasion* / drug effects
  • Immune Evasion* / immunology
  • Immunity, Innate
  • Proviruses / genetics
  • Proviruses / immunology
  • RNA, Viral / genetics
  • RNA, Viral / immunology
  • Reverse Transcription / drug effects
  • Reverse Transcription / immunology
  • Viral Regulatory and Accessory Proteins / genetics
  • Viral Regulatory and Accessory Proteins / metabolism
  • Virus Internalization / drug effects
  • Virus Release / drug effects
  • Virus Release / immunology
  • Virus Replication / drug effects
  • Virus Replication / genetics
  • Virus Replication / immunology

Substances

  • Viral Regulatory and Accessory Proteins
  • Anti-HIV Agents
  • Antigens, Differentiation
  • Cytokines
  • RNA, Viral