Enhanced human immunodeficiency virus Type 1 expression and neuropathogenesis in knockout mice lacking Type I...

Area of Science:

• Neurovirology
• Immunology
• Infectious Diseases

Background:

• The role of Type I interferon (IFN) in human immunodeficiency virus Type 1 (HIV-1) neuropathogenesis is not well understood, with conflicting reports on its effects.
• Both protective and detrimental roles of IFN signaling in HIV-1 infection have been suggested.

Purpose of the Study:

• To investigate the impact of Type I IFN signaling on HIV-1 brain infection and neuropathogenesis.
• To analyze HIV-1 progression in mice lacking the Type I IFN receptor (IFNRKO).

Main Methods:

• Genetically modified mice (IFNRKO) and wild-type (WT) littermates were infected with EcoHIV, a chimeric HIV-1.
• Systemic infection and direct intracerebral injection models were used.
• Neuropathogenesis was assessed using histopathology, immunohistochemistry, immunofluorescence, and PCR analyses of brain tissue.

Main Results:

• IFNRKO mice exhibited higher HIV-1 expression in peripheral macrophages and increased viral entry into the brain compared to WT mice.
• Both IFNRKO and WT mice developed HIV-1-associated brain lesions, including microglial activation and astrocytosis.
• Key parameters of neuropathogenesis, such as HIV-1 replication in microglia/macrophages, were significantly exacerbated in IFNRKO mice.

Conclusions:

• Type I IFN signaling demonstrably limits HIV-1 infection and pathogenesis within the mouse brain.
• Absence of Type I IFN receptor signaling leads to increased viral burden and neuropathology.