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
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.
"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. "
[Show abstract][Hide abstract] 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.
"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). "
[Show abstract][Hide abstract] 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.
PLoS ONE 01/2011; 6(1):e16145. DOI:10.1371/journal.pone.0016145 · 3.23 Impact Factor
"Several epidemiological studies have shown that active HSV-2 infection is associated with an increased risk of HIV acquisition (Boulos et al., 1992; Hook et al., 1992; Corey et al., 2004). Although mechanical disruption of mucous membranes is the major risk factor for increased HIV acquisition, local recruitment and activation of CD4 T cells (Cunningham et al., 1985) and macrophages (Kucera et al., 1990; Heng et al., 1994) increase the number of target cells for HIV entry. HSV promotes HIV replication in human T cells (Mosca et al., 1987) and in macrophages by inducing NF-κB activity (Moriuchi et al., 2000). "
[Show abstract][Hide abstract] ABSTRACT: Antecedent or current infections can alter the immunopathologic outcome of a subsequent unrelated infection. Immunomodulation by co-infecting pathogens has been referred to as 'heterologous immunity' and has been postulated to play a role in host susceptibility to disease, tolerance to organ transplant, and autoimmune disease. The effect of various infections on heterologous immune responses has been well studied in the context of shared epitopes and cross-reactive T cells. It has been shown that prior infections can modulate protective immunity and immunopathology by forming a pool of memory T cells that can cross-react with antigens from heterologous organisms or through the generation of a network of regulatory cells and cytokines. While it is not feasible to alter a host's history of prior infection, understanding heterologous immune responses in the context of simultaneous unrelated infections could have important therapeutic implications. Here, we outline key evidence from animal and human studies demonstrating the effect of heterologous immunity on the outcome of disease. We briefly review the role of T cells, but expand our discussion to explore other immune mechanisms that may modulate the response to concurrent active infections. In particular, we underscore the role of the innate immune system, polarized responses and regulatory mechanisms on heterologous immune responses.
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