Primary Infection of Human Herpesvirus 6 in Children with Vertical Infection of Human Immunodeficiency Virus Type 1

Kositanont, Uraiwan; Wasi, Chantapong; Wanprapar, Nirun; Bowonkiratikachorn, Piyaporn; Chokephaibulkit, Kulkunya; Chearskul, Sanay; Chimabutra, Kanittha; Sutthent, Ruengpung; Foongladda, Suporn; Inagi, Reiko; Kurata, Takeshi; Yamanishi, Koichi

doi:10.1086/314826

Cited by 46 publications

(19 citation statements)

References 21 publications

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“…The mechanism underlying HHV-6-mediated CD4 upregulation seems to involve direct activation of the CD4 promoter in HHV-6-infected cells (4), as indirectly confirmed by the lack of bystander effect observed in our system. The ability of HHV-6 to upregulate CD4 expression was fingered as one of the major mechanisms of positive interaction of HHV-6 with HIV, as CD4 is the primary HIV receptor molecule, corroborating the hypothesis of a putative cofactorial role of HHV-6 in AIDS (15,19). Despite the evidence hitherto accumulated, however, definitive proof of the role played by HHV-6 in AIDS is still wanting.…”

Section: Discussionmentioning

confidence: 87%

Pathogenic Effects of Human Herpesvirus 6 in Human Lymphoid Tissue Ex Vivo

Grivel

Santoro²,

Chen

et al. 2003

J Virol

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Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive agent that has been suggested to act as a cofactor in the progression of human immunodeficiency virus disease. However, the lack of suitable experimental models has hampered the elucidation of the mechanisms of HHV-6-mediated immune suppression. Here, we used ex vivo lymphoid tissue to investigate the cellular tropism and pathogenic mechanisms of HHV-6. Viral strains belonging to both HHV-6 subgroups (A and B) were able to productively infect human tonsil tissue fragments in the absence of exogenous stimulation. The majority of viral antigen-expressing cells were CD4؉ T lymphocytes expressing a nonnaive phenotype, while CD8 ؉ T cells were efficiently infected only with HHV-6A. Accordingly, HHV-6A infection resulted in the depletion of both CD4؉ and CD8 ؉ T cells, whereas in HHV-6B-infected tissue CD4 ؉ T cells were predominantly depleted. The expression of different cellular antigens was dramatically altered in HHV-6-infected tissues: whereas CD4 was upregulated, both CD46, which serves as a cellular receptor for HHV-6, and CD3 were downmodulated. However, CD3 downmodulation was restricted to infected cells, while the loss of CD46 expression was generalized. Moreover, HHV-6 infection markedly enhanced the production of the CC chemokine RANTES, whereas other cytokines and chemokines were only marginally affected. These results provide the first evidence, in a physiologically relevant study model, that HHV-6 can severely affect the physiology of secondary lymphoid organs through direct infection of T lymphocytes and modulation of key membrane receptors and chemokines.

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Section: Discussionmentioning

confidence: 87%

Pathogenic Effects of Human Herpesvirus 6 in Human Lymphoid Tissue Ex Vivo

Grivel

Santoro²,

Chen

et al. 2003

J Virol

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“…In another study, 41 HIV-positive infants were carefully monitored during the first year of life. Lower CD4 ϩ cell numbers resulted in lower rates of primary HHV-6 infection, and those children acquiring HHV-6 showed a more rapid progression towards AIDS (222).…”

Section: Clinical Manifestations Of Hhv-6 Infectionmentioning

confidence: 99%

Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy

2005

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Human herpesvirus 6 (HHV-6) is a betaherpesvirus that is closely related to human cytomegalovirus. It was discovered in 1986, and HHV-6 literature has expanded considerably in the past 10 years. We here present an up-to-date and complete overview of the recent developments concerning HHV-6 biological features, clinical associations, and therapeutic approaches. HHV-6 gene expression regulation and gene products have been systematically characterized, and the multiple interactions between HHV-6 and the host immune system have been explored. Moreover, the discovery of the cellular receptor for HHV-6, CD46, has shed a new light on HHV-6 cell tropism. Furthermore, the in vitro interactions between HHV-6 and other viruses, particularly human immunodeficiency virus, and their relevance for the in vivo situation are discussed, as well as the transactivating capacities of several HHV-6 proteins. The insight into the clinical spectrum of HHV-6 is still evolving and, apart from being recognized as a major pathogen in transplant recipients (as exemplified by the rising number of prospective clinical studies), its role in central nervous system disease has become increasingly apparent. Finally, we present an overview of therapeutic options for HHV-6 therapy (including modes of action and resistance mechanisms)

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“…In vitro, HHV-6A was shown to: i) replicate primarily in CD4 + T cells and cause their destruction in synergy with HIV-1 [8]; ii) transactivate the HIV-1 long terminal repeat [9]; iii) induce de novo CD4 expression and HIV-1 susceptibility in otherwise HIV-refractory cells such as CD8 + T lymphocytes and NK cells [10,11]; and iv) augment the release of HIV-1-enhancing inflammatory cytokines [12]. In vivo studies have documented: i) widespread HHV-6 infection in patients with full-blown AIDS at post-mortem examination [13,14]; ii) frequent reactivation of HHV-6 in early symptomatic HIV-1-infected subjects [15]; iii) vigorous HHV-6 replication in lymph nodes of HIV-1-infected subjects, associated with an increased local HIV-1 load [16,17]; and iv) accelerated progression of HIV-1 disease in infants who acquire HHV-6 within the first year of life [18]. In addition, we recently provided evidence that in vivo coinfection with HHV-6A accelerates the course of simian immunodeficiency virus (SIV) disease in pig-tailed macaques (M. nemestrina) [19].…”

Section: Introductionmentioning

confidence: 99%

Evolution of SIV toward RANTES resistance in macaques rapidly progressing to AIDS upon coinfection with HHV-6A

et al. 2009

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Background: Progression to AIDS is often associated with the evolution of HIV-1 toward increased virulence and/or pathogenicity. Evidence suggests that a virulence factor for HIV-1 is resistance to CCR5-binding chemokines, most notably RANTES, which are believed to play a role in HIV-1 control in vivo. HIV-1 can achieve RANTES resistance either by phenotypic switching from an exclusive CCR5 usage to an expanded coreceptor specificity, or by the acquisition of alternative modalities of CCR5 usage. An infectious agent that might promote the evolution of HIV-1 toward RANTES resistance is human herpesvirus 6A (HHV-6A), which is frequently reactivated in HIV-1-infected patients and is a potent RANTES inducer in lymphoid tissue.

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Primary Infection of Human Herpesvirus 6 in Children with Vertical Infection of Human Immunodeficiency Virus Type 1

Cited by 46 publications

References 21 publications

Pathogenic Effects of Human Herpesvirus 6 in Human Lymphoid Tissue Ex Vivo

Pathogenic Effects of Human Herpesvirus 6 in Human Lymphoid Tissue Ex Vivo

Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy

Evolution of SIV toward RANTES resistance in macaques rapidly progressing to AIDS upon coinfection with HHV-6A

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