Herpes simplex virus type 2-infected dendritic cells produce TNF-α, which enhances CCR5 expression and stimulates HIV production from adjacent infected cells

• Published in: The Journal of immunology (1950) 2015-05, Vol.194 (9), p.4438-4445
• Main Authors: Marsden, Valerie, Donaghy, Heather, Bertram, Kirstie M, Harman, Andrew N, Nasr, Najla, Keoshkerian, Elizabeth, Merten, Steven, Lloyd, Andrew R, Cunningham, Anthony L
• Format: Article
• Language: English
• Subjects: Coinfection; Culture Media, Conditioned - metabolism; Cytokines - biosynthesis; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - virology; Gene Expression Regulation; Herpes Genitalis - genetics; Herpes Genitalis - immunology; Herpes Genitalis - metabolism; Herpes simplex virus 2; Herpesvirus 2, Human - physiology; Herpesvirus 2, Human - radiation effects; HIV Infections - genetics; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - virology; HIV-1 - physiology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Models, Biological; Receptors, CCR5 - genetics; Receptors, CCR5 - metabolism; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation; Virus Replication
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1401706

Prior HSV-2 infection enhances the acquisition of HIV-1 >3-fold. In genital herpes lesions, the superficial layers of stratified squamous epithelium are disrupted, allowing easier access of HIV-1 to Langerhans cells (LC) in the epidermis and perhaps even dendritic cells (DCs) in the outer dermis, as well as to lesion infiltrating activated T lymphocytes and macrophages. Therefore, we examined the effects of coinfection with HIV-1 and HSV-2 on monocyte-derived DCs (MDDC). With simultaneous coinfection, HSV-2 significantly stimulated HIV-1 DNA production 5-fold compared with HIV-1 infection alone. Because