Changes in Natural Killer cell activation and function during primary HIV-1 Infection

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Natural Killer (NK) cells are implicated in the pathogenesis of primary HIV-1 infection.
• HIV infection is known to dysregulate NK-cell responses.
• Understanding the bidirectional relationship between HIV and NK cells is crucial for managing primary infection.

Purpose of the Study:

• To dissect the bi-directional relationship between HIV and NK cells during primary HIV-1 infection.
• To understand how HIV impacts NK-cell responses in the early stages of infection.

Main Methods:

• Analysis of paired samples from 41 high-risk, initially HIV-uninfected participants before and during primary HIV-1 infection.
• Flow cytometry to assess NK and T-cell activation, NK-cell receptor expression, cytotoxic and cytokine-secretory functions, and trafficking markers (CCR7, α(4)β(7)).
• Non-parametric statistical tests were employed to analyze the data.

Main Results:

• Both NK cells and T-cells showed significant activation post-HIV acquisition, but their activation became uncoupled after infection.
• NK-cell and T-cell activation correlated with HIV viral load during primary infection.
• Increased frequency of Killer Immunoglobulin-like Receptor (KIR)-expressing NK cells was observed, with KIR(pos) NK cells showing less activation.
• Cytotoxic NK cell responses were impaired during HIV-1 infection, while IFN-γ secretory function remained unaltered.
• Elevated frequency of CCR7+ NK cells, indicative of lymph node trafficking, was noted during primary infection.

Conclusions:

• Primary HIV-1 infection leads to increased NK-cell activation and KIR expression, coupled with reduced NK-cell cytotoxicity.
• The rise in NK cells capable of trafficking to lymph nodes suggests a potential role in secondary lymphoid tissue immune events.
• These findings highlight the complex interplay between HIV and NK-cell immunity during acute infection.