Human Immunodeficiency Virus (HIV-1) Targets Astrocytes via Cell-Free and Cell-Associated Infection

Area of Science:

• Neurovirology
• Cell Biology
• Infectious Diseases

Background:

• Human Immunodeficiency Virus type 1 (HIV-1) infection of astrocytes is debated, despite in vivo evidence of viral DNA.
• Primary human astrocytes are investigated for their susceptibility to HIV-1 infection.

Purpose of the Study:

• To investigate potential pathways for astrocyte infection by HIV-1.
• To determine if astrocytes can produce infectious HIV-1 particles.

Main Methods:

• Primary human astrocytes from neuroprogenitor cells (NPCs) and induced pluripotent stem cells (iPSCs) expressing CXCR4 and CCR5 coreceptors were used.
• Astrocytes were infected with cell-free HIV-1 or cell-associated HIV-1 via infected macrophages/microglia.

Main Results:

• Cell-free HIV-1 showed low-level infectivity, primarily due to entry defects.
• Pseudotyped viruses, bypassing specific receptor entry, led to productive astrocyte infection and release of infectious HIV-1 particles.

Conclusions:

• Astrocytes may contribute to neurotoxicity in HIV-associated neurocognitive disorders (HAND).
• Astrocytes could serve as reservoirs for HIV in the central nervous system (CNS).