Effect of multiple herpesvirus infections on the progression of HIV disease in a cohort of HIV seroconverters

Suligoi, Barbara; Dorrucci, Maria; Uccella, Ilaria; Andreoni, Massimo; Rezza, Giovanni

doi:10.1002/jmv.10281

Cited by 11 publications

(19 citation statements)

References 37 publications

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“…Some epidemiological studies have also found a positive correlation between KSHV coinfection and progression to AIDS, suggesting that KSHV may likewise influence the biology of HIV (11,12). Indeed, KSHV infection of HIV-infected monocytic cell lines or peripheral blood mononuclear cells isolated from HIV-infected individuals induces HIV reactivation from a latent state (13).…”

mentioning

confidence: 99%

Kaposi's Sarcoma-Associated Herpesvirus ORF45 Mediates Transcriptional Activation of the HIV-1 Long Terminal Repeat via RSK2

Karijolich

Zhao

Peterson

et al. 2014

J Virol

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Robust activation of human immunodeficiency virus type 1 (HIV-1) gene expression occurs upon superinfection with Kaposi's sarcoma-associated herpesvirus (KSHV), a common AIDS-associated pathogen. Though the mechanisms underlying this phenotype remain unknown, several KSHV-encoded factors have been reported to stimulate HIV-1 long terminal repeat (LTR) activity. Here, we systematically evaluated the ability of KSHV tegument proteins to modulate the activation of an integrated HIV-1 LTR and revealed that the most potent individual activator is ORF45. ORF45 directs an increase in RNA polymerase II recruitment to the HIV-1 LTR, leading to enhanced transcriptional output. ORF45 is a robust activator of the p90 ribosomal S6 kinases (RSK), and we found that this activity is necessary but not sufficient to increase transcription from the LTR. Of the three widely expressed RSK isoforms, RSK2 appears to be selectively involved in LTR stimulation by both KSHV ORF45 and HIV-1 Tat. However, constitutively active RSK2 is unable to stimulate the LTR, suggesting that ORF45 may preferentially direct this kinase to a specific set of targets. Collectively, our findings reveal a novel transcriptional activation function for KSHV ORF45 and highlight the importance of RSK2 in shaping the transcriptional environment during infection. IMPORTANCE Kaposi's sarcoma-associated herpesvirus (KSHV) is a prominent AIDS-associated pathogen. Previous studies have shown that infection of cells containing human immunodeficiency virus type 1 (HIV-1) with KSHV leads to potent stimulation of HIV-1 gene expression by activating the HIV-1 promoter, termed the long terminal repeat (LTR).Here, we compared the abilities of various KSHV proteins to activate gene expression from the HIV-1 LTR and found that KSHV ORF45 is the most potent activator. ORF45 is known to induce cell signaling through ribosomal S6 kinase (RSK) and enhance protein translation. However, we revealed that the activation of a specific isoform of RSK by ORF45 also leads to increased mRNA synthesis from the LTR by the host RNA polymerase. Collectively, our findings provide new insight into the interviral interactions between KSHV and HIV that may ultimately impact disease.

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mentioning

confidence: 99%

Kaposi's Sarcoma-Associated Herpesvirus ORF45 Mediates Transcriptional Activation of the HIV-1 Long Terminal Repeat via RSK2

Karijolich

Zhao

Peterson

et al. 2014

J Virol

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“…An effective HSV-1 live-virus vaccine may reduce the incidence of multiple serious diseases, including some cases of genital ulcer disease, thereby reducing the rates of HIV acquisition and transmission (37).…”

Section: Discussionmentioning

confidence: 99%

“…Complications of HSV infection include meningitis, encephalitis, esophagitis, disseminated disease in neonates and immunocompromised individuals, and herpes stromal keratitis, which can lead to blindness. Additionally, HSV-2 infection increases human immunodeficiency virus (HIV) acquisition and transmission rates more than twofold, enhances HIV replication, and speeds progression to AIDS (7,18,37). Despite the significant morbidity and mortality associated with HSV infections, no effective vaccines are available.…”

mentioning

confidence: 99%

A Replication-Competent, Neuronal Spread-Defective, Live Attenuated Herpes Simplex Virus Type 1 Vaccine

Brittle

Wang

Lubinski

et al. 2008

J Virol

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Herpes simplex virus type 1 (HSV-1) produces oral lesions, encephalitis, keratitis, and severe infections in the immunocompromised host. HSV-1 is almost as common as HSV-2 in causing first episodes of genital herpes, a disease that is associated with an increased risk of human immunodeficiency virus acquisition and transmission. No approved vaccines are currently available to protect against HSV-1 or HSV-2 infection. We developed a novel HSV vaccine strategy that uses a replication-competent strain of HSV-1, NS-gEnull, which has a defect in anterograde and retrograde directional spread and cell-to-cell spread. Following scratch inoculation on the mouse flank, NS-gEnull replicated at the site of inoculation without causing disease. Importantly, the vaccine strain was not isolated from dorsal root ganglia (DRG). We used the flank model to challenge vaccinated mice and demonstrated that NS-gEnull was highly protective against wild-type HSV-1. The challenge virus replicated to low titers at the site of inoculation; therefore, the vaccine strain did not provide sterilizing immunity. Nevertheless, challenge by HSV-1 or HSV-2 resulted in less-severe disease at the inoculation site, and vaccinated mice were totally protected against zosteriform disease and death. After HSV-1 challenge, latent virus was recovered by DRG explant cocultures from <10% of vaccinated mice compared with 100% of mock-vaccinated mice. The vaccine provided protection against disease and death after intravaginal challenge and markedly lowered the titers of the challenge virus in the vagina. Therefore, the HSV-1 gEnull strain is an excellent candidate for further vaccine development.Herpes simplex virus type 1 (HSV-1) and HSV-2 are closely related alphaherpesviruses that cause lifelong infections for which there is no cure. HSV-1 generally causes oral lesions, while HSV-2 remains the most common cause of genital ulcers; however, the epidemiology of genital herpes is changing in that 35% to 50% of new cases are now caused by HSV-1 (40). The life cycles of HSV-1 and HSV-2 are similar. After replication in epithelial cells, HSV enters local sensory nerve endings of the peripheral nervous system and spreads in a retrograde direction to neuronal cell bodies. HSV then spreads to adjacent neurons in ganglia, where a lifelong latent infection is established (43). During recurrences, HSV travels in the anterograde direction along axon fibers from infected neuronal cell bodies to skin or mucosal surfaces, resulting in asymptomatic virus shedding or symptomatic vesicles and ulcers.More than 70% of people in the United States are seropositive for HSV-1 or HSV-2 by age 49, with HSV-1 being more prevalent (44). Worldwide, the prevalence of infection is generally higher than in the United States (34). Complications of HSV infection include meningitis, encephalitis, esophagitis, disseminated disease in neonates and immunocompromised individuals, and herpes stromal keratitis, which can lead to blindness. Additionally, HSV-2 infection increases human immunodeficienc...

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“…1 On the other hand, it is growing evidence that herpevirus infection may increase an pasienal's susceptibility to HIV infection, 2 and could interact with HIV to accelerate disease progression. 3,4 To date, there are eight known human herpes viruses, they are herpes simplex virus type 1 (HSV-1), HSV-2, varicella-zoster virus (VZV), and cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpesvirus-6, human herpesvirus-7, and HHV-8 (Kaposi's sarcoma herpes virus). 5 Among herpesviruses family members, HSV is the most common co-infection and pathogenic in HIV-1-positive patients.…”

Section: Introductionmentioning

confidence: 99%

Seroprevalence of Herpes Simplex virus types 1 and 2 and their association with CD4 count among HIV-positive patients

Sufiawati

Widyaputra

Djajakusumah

2012

Dent. J. (Majalah Kedokteran Gigi)

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Background: Herpes simplex virus (HSV) is a common cause of viral opportunistic infections among HIV t-tests and analysis of variance (ANOVA). Results: There were no significant differences in HSV-1 seroprevalence between HIV-positive patients (71%) and HIV-negative patients (66%). HSV-2 seroprevalence was significantly higher in HIV-positive patients (30%) than HIV-negative patients (5%). The titers of HSV-1 IgG antibodies in HIV-positive patients (mean 24.63 ± 19.06 IDU) were significantly lower than those of HIV-negative patients (mean 44.62 ± 33.22 IDU). In contrast, HSV-2 IgG antibody titers in HIV-positive patients (mean 13.31 ± 20.28 IDU) were significantly higher than HIV-negative patients (mean 4.42 ± 10.99 IDU)

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Effect of multiple herpesvirus infections on the progression of HIV disease in a cohort of HIV seroconverters

Cited by 11 publications

References 37 publications

Kaposi's Sarcoma-Associated Herpesvirus ORF45 Mediates Transcriptional Activation of the HIV-1 Long Terminal Repeat via RSK2

Kaposi's Sarcoma-Associated Herpesvirus ORF45 Mediates Transcriptional Activation of the HIV-1 Long Terminal Repeat via RSK2

A Replication-Competent, Neuronal Spread-Defective, Live Attenuated Herpes Simplex Virus Type 1 Vaccine

Seroprevalence of Herpes Simplex virus types 1 and 2 and their association with CD4 count among HIV-positive patients

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