Human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 2 (HSV-2) can coinfect and simultaneously replicate in the same human CD4+ cell: Effect of coinfection on infectious HSV-2 and HIV-1 replication
Department of Microbiology and Immunology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27103. AIDS Research and Human Retroviruses
(Impact Factor: 2.33).
Experiments were designed to determine whether HIV-1 and herpes simplex virus type 2 (HSV-2) coinfection leads to simultaneous replication of both viruses in the same human CD4+ cell (MT-4 cell line) and the possible effects of coinfection on infectious virus production. Results from transmission electron microscopy analysis revealed replication of typical HSV-2 nucleocapsids in the nucleus and budding of HIV-1 particles through the plasma membrane and through intracytoplasmic vacuoles containing enveloped HSV-2 particles in the same coinfected cell. Coinfection of HIV-1 persistently infected H9IIIB or promonocytic U1 cells with HSV-2 did not alter total production of infectious HSV-2 or the percentage of HSV-2 infectious centers compared with control H9 and U937 cells infected with HSV-2 alone. However, in coinfected promonocytic U1 cells HSV-2 induced infectious HIV-1 production measured by syncytial plaque assay. In summary, both HIV-1 and HSV-2 can coinfect and simultaneously replicate in the same human CD4+ cell. Interactions between HIV-1 and HSV-2 appear to be unidirectional, resulting in accelerated replication of HIV-1 as reported by Albrecht et al. (J Virol 1989;63:1861-1868), but not HSV-2 as shown by us.
Available from: Robert J Carpenter
- "HSV- 2 and HIV-1 can infect the same cells, and HSV-2 proteins ICP-10, ICP-27, and ICP-4 have been shown to upregulate HIV-1 replication by their interactions with the HIV-1 LTR region. Further, HSV-2 protein 16 interacts with the HIV-1 Tat protein and increases HIV-1 transcription     . As a result, HSV-2 may not only enhance HIV-1 transmission, but it may also have a significant impact on HIV-1 viral control and disease progression among coinfected patients. "
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ABSTRACT: Due to shared routes of infection, HIV-infected persons are frequently coinfected with other sexually transmitted infections (STIs). Studies have demonstrated the bidirectional relationships between HIV and several STIs, including herpes simplex virus-2 (HSV-2), hepatitis B and C viruses, human papilloma virus, syphilis, gonorrhea, chlamydia, and trichomonas. HIV-1 may affect the clinical presentation, treatment outcome, and progression of STIs, such as syphilis, HSV-2, and hepatitis B and C viruses. Likewise, the presence of an STI may increase both genital and plasma HIV-1 RNA levels, enhancing the transmissibility of HIV-1, with important public health implications. Regarding the effect of STIs on HIV-1 progression, the most studied interrelationship has been with HIV-1/HSV-2 coinfection, with recent studies showing that antiherpetic medications slow the time to CD4 <200 cells/µL and antiretroviral therapy among coinfected patients. The impact of other chronic STIs (hepatitis B and C) on HIV-1 progression requires further study, but some studies have shown increased mortality rates. Treatable, nonchronic STIs (i.e., syphilis, gonorrhea, chlamydia, and trichomonas) typically have no or transient impacts on plasma HIV RNA levels that resolve with antimicrobial therapy; no long-term effects on outcomes have been shown. Future studies are advocated to continue investigating the complex interplay between HIV-1 and other STIs.
Available from: Hakim Hocini
- "A 12-fold increase in p24 antigen expression was observed in ACH-2 cells treated with crude supernatants from HSV-2-infected cells relative to the control (Figure 4D). As HSV-2 itself can reactivate latent HIV-1 , infectious particles were removed from the supernatants by ultracentrifugation. As expected, HIV reactivation was lowered in the presence of virion-free supernatants but remained still significant compared to the control (Figure 4D). "
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ABSTRACT: High mobility group box 1 protein (HMGB1) is a major endogenous danger signal that triggers inflammation and immunity during septic and aseptic stresses. HMGB1 recently emerged as a key soluble factor in the pathogenesis of various infectious diseases, but nothing is known of its behaviour during herpesvirus infection. We therefore investigated the dynamics and biological effects of HMGB1 during HSV-2 infection of epithelial HEC-1 cells.
Despite a transcriptional shutdown of HMGB1 gene expression during infection, the intracellular pool of HMGB1 protein remained unaffected, indicating its remarkable stability. However, the dynamics of HMGB1 was deeply modified in infected cells. Whereas viral multiplication was concomitant with apoptosis and HMGB1 retention on chromatin, a subsequent release of HMGB1 was observed in response to HSV-2 mediated necrosis. Importantly, extracellular HMGB1 was biologically active. Indeed, HMGB1-containing supernatants from HSV-2 infected cells induced the migration of fibroblasts from murine or human origin, and reactivated HIV-1 from latently infected T lymphocytes. These effects were specifically linked to HMGB1 since they were blocked by glycyrrhizin or by a neutralizing anti-HMGB1 antibody, and were mediated through TLR2 and the receptor for Advanced Glycation End-products (RAGE). Finally, we show that genital HSV-2 active infections also promote HMGB1 release in vivo, strengthening the clinical relevance of our experimental data.
These observations target HMGB1 as an important actor during HSV-2 genital infection, notably in the setting of HSV-HIV co-infection.
Available from: Philippe Mayaud
- "Support for the biological plausibility of this mechanism comes from several lines of evidence. First, electron microscopy studies have shown that HSV-2 and HIV can simultaneously infect the same cells, including CD4 + T-lymphocytes. Second, HSV proteins have been shown to up-regulate HIV replication in vitro, mainly through a mechanism of reactivation of the HIV long terminal repeat (LTR)272829. "
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