HSV-2 Cellular Programming Enables Productive HIV Infection in Dendritic Cells

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Genital herpes simplex virus type 2 (HSV-2) is a common STI.
• HSV-2 infection increases HIV-1 acquisition and transmission risk.
• Dendritic cells (DCs) are crucial in initial mucosal responses to HSV-2 and HIV-1.

Purpose of the Study:

• To investigate mechanisms of HSV-2-mediated enhancement of HIV-1 infection in DCs.
• To understand how HSV-2 alters DC function to promote HIV-1 replication.

Main Methods:

• Investigated HSV-2 and HIV-1 co-infection in human DCs.
• Analyzed cellular signaling pathways, including cGAS-STING.
• Measured protein expression of restriction factors and signaling molecules.

Main Results:

• HSV-2 enhanced productive HIV-1 infection in DCs, requiring intact viral DNA.
• The cGAS-STING pathway was involved, but TLR2, TLR3, and IFN-β were not.
• HSV-2 decreased expression of key HIV-1 restriction factors (SAMHD1, TREX1, APOBEC3G) via STING activation.

Conclusions:

• HSV-2 reprograms DCs, increasing their susceptibility to HIV-1 infection.
• This reprogramming involves the cGAS-STING pathway and degradation of restriction factors.
• HSV-2 creates a cellular environment conducive to HIV-1 infection and transmission.