Human cytomegalovirus and human immunodeficiency virus type-1 co-infection in human cervical tissue

Area of Science:

• Virology
• Immunology
• Reproductive Health

Background:

• Human cytomegalovirus (HCMV) and human immunodeficiency virus type-1 (HIV-1) are prevalent in the female genital tract.
• Understanding their interaction and pathogenesis in this compartment is crucial for public health.

Purpose of the Study:

• To establish and utilize a human cervical explant model for studying single and dual infections by HCMV and HIV-1.
• To investigate the impact of co-infection on viral replication and host immune responses.

Main Methods:

• Development of a human cervical explant model.
• Infection with HCMV strains (one GFP-expressing, two clinical) and HIV-1(Ba-L).
• Quantification of viral DNA and p24 antigen, cytokine analysis (IL-6, IL-8, GRO-alpha), immunohistochemistry, and flow cytometry.

Main Results:

• Peak HCMV DNA copies observed 14–21 days post-infection; peak HIV-1 p24 antigen at 7 days.
• HIV-1(Ba-L) appeared to enhance HCMV replication in co-infected tissues.
• Both single and dual infections increased pro-inflammatory cytokine levels (IL-6, IL-8, GRO-alpha).
• HCMV infected leukocytes (CD45+/CD1a+/CD14+/HLA-DR+), not stromal or endothelial cells.
• Cells positive for both GFP (HCMV) and HIV-1 p24 antigen were detected in co-infected tissues.

Conclusions:

• The human cervical explant model effectively simulates in vivo viral dynamics and interactions.
• Co-infection with HIV-1 may enhance HCMV replication in the female genital tract.
• These viral infections induce significant inflammatory responses, mediated by infected leukocytes.