HIV-host interactome revealed directly from infected cells

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Human immunodeficiency virus type 1 (HIV-1) relies on host cellular machinery for replication.
• Understanding viral protein interactions with host factors is crucial for developing antiviral strategies.

Purpose of the Study:

• To identify host protein interactomes of HIV-1 Env and Vif proteins during natural infection.
• To discover novel targets for antiviral interventions.

Main Methods:

• Transposon-mediated saturation linker scanning mutagenesis to generate tagged HIV-1 isolates.
• Differential isotopic labeling and affinity-capture mass spectrometry on human lymphocyte cultures.
• Analysis of viral protein associations during viral replication cycles.

Main Results:

• Identified host associations with trimerized Env during biosynthesis, at virological synapses, with innate immune effectors (e.g., HLA-E), and signaling pathways (e.g., Notch1).
• Defined Vif associations with host proteins regulating nuclear transcription, nucleoside biosynthesis, and protein degradation.
• Recovered interacting proteins without bias, irrespective of their impact on viral replication.

Conclusions:

• The study provides a comprehensive map of HIV-1 Env and Vif protein interactomes during infection.
• These identified host-pathogen interactions offer strategic targets for novel antiviral therapies.
• The methodology is broadly applicable for elucidating other pathogen-host interactomes.