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.
Copyright © 2025 Elsevier Ltd. All rights reserved.
Publication types
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Review
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-HIV Agents / pharmacology
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Anti-HIV Agents / therapeutic use
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Antigens, Differentiation
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Capsid / drug effects
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Capsid / immunology
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Cytokines
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Genome, Viral
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HIV Infections* / drug therapy
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HIV Infections* / immunology
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HIV Infections* / virology
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HIV-1* / drug effects
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HIV-1* / genetics
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HIV-1* / immunology
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HIV-1* / physiology
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Host-Pathogen Interactions* / drug effects
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Host-Pathogen Interactions* / genetics
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Host-Pathogen Interactions* / immunology
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Humans
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Immune Evasion* / drug effects
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Immune Evasion* / immunology
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Immunity, Innate
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Proviruses / genetics
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Proviruses / immunology
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RNA, Viral / genetics
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RNA, Viral / immunology
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Reverse Transcription / drug effects
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Reverse Transcription / immunology
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Viral Regulatory and Accessory Proteins / genetics
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Viral Regulatory and Accessory Proteins / metabolism
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Virus Internalization / drug effects
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Virus Release / drug effects
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Virus Release / immunology
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Virus Replication / drug effects
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Virus Replication / genetics
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Virus Replication / immunology
Substances
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Viral Regulatory and Accessory Proteins
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Anti-HIV Agents
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Antigens, Differentiation
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Cytokines
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RNA, Viral