NK cell activity controls human herpesvirus 8 latent infection and is restored upon highly active antiretroviral therapy in AIDS patients with regressing Kaposi's sarcoma

Sirianni, Maria Caterina; Vincenzi, Laura; Topino, Simone; Giovannetti, Antonello; Mazzetta, Francesca; Libi, Fabio; Scaramuzzi, Donato; Andreoni, Massimo; Pinter, Elena; Baccarini, Sara; Rezza, Giovanni; Monini, Paolo; Ensoli, Barbara

doi:10.1002/1521-4141(2002010)32:10<2711::aid-immu2711>3.0.co;2-3

Cited by 72 publications

(50 citation statements)

References 37 publications

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“…HAART also restores anti-PEL natural killer (NK) cell lytic activity in AIDS-associated KS patients (469). This immune restoration is associated with loss of detection of KSHV DNA in PBMCs in these patients.…”

Section: Aids-associated Ksmentioning

confidence: 99%

“…Nonresponders also failed to recover NK activity with respect to cells latently infected with KSHV (PEL cells) and failed to clear KSHV from PBMCs (469). A case report clearly demonstrated the inverse relationship between HAART and KS: after 6 years of antiretroviral therapy, including 3 years of HAART, KSHV DNA became undetectable in PBMCs (388).…”

Section: Aids-associated Ksmentioning

confidence: 99%

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Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Dourmishev

Palmeri

et al. 2003

Microbiol Mol Biol Rev

309

367

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Kaposi's sarcoma had been recognized as unique human cancer for a century before it manifested as an AIDS-defining illness with a suspected infectious etiology. The discovery of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, in 1994 by using representational difference analysis, a subtractive method previously employed for cloning differences in human genomic DNA, was a fitting harbinger for the powerful bioinformatic approaches since employed to understand its pathogenesis in KS. Indeed, the discovery of KSHV was rapidly followed by publication of its complete sequence, which revealed that the virus had coopted a wide armamentarium of human genes; in the short time since then, the functions of many of these viral gene variants in cell growth control, signaling apoptosis, angiogenesis, and immunomodulation have been characterized. This critical literature review explores the pathogenic potential of these genes within the framework of current knowledge of the basic herpesvirology of KSHV, including the relationships between viral genotypic variation and the four clinicoepidemiologic forms of Kaposi's sarcoma, current viral detection methods and their utility, primary infection by KSHV, tissue culture and animal models of latent- and lytic-cycle gene expression and pathogenesis, and viral reactivation from latency. Recent advances in models of de novo endothelial infection, microarray analyses of the host response to infection, receptor identification, and cloning of full-length, infectious KSHV genomic DNA promise to reveal key molecular mechanisms of the candidate pathogeneic genes when expressed in the context of viral infection

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Section: Aids-associated Ksmentioning

confidence: 99%

Section: Aids-associated Ksmentioning

confidence: 99%

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Dourmishev

Palmeri

et al. 2003

Microbiol Mol Biol Rev

309

367

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“…In immune-competent individuals, NK cells target and lyse latent KSHV-infected cells (7). In contrast, insufficient NK activity is associated with severe, chronic, and recurrent disseminating herpesvirus infections (8,9), including herpessimplex, Epstein-Barr, varicella zoster, and cytomegalovirus, and is observed in several solid tumor malignancies (10,11), including CKS (12,13).…”

Section: Introductionmentioning

confidence: 99%

A Common Genetic Variant inFCGR3A-V158F and Risk of Kaposi Sarcoma Herpesvirus Infection and Classic Kaposi Sarcoma

Brown

Fallin

Goedert

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Associations of FCGR3A among men with HIV/acquired immunodeficiency syndrome suggest that host responses affect the pathogenesis of Kaposi sarcoma herpesvirus (KSHV) infection and risk of acquired immunodeficiency syndrome -associated Kaposi sarcoma. Using DNA from two HIV seronegative case-control populations in Italy, we examined whether the functional FCGR3A-V158F variant was associated with risk of KSHV infection or classic Kaposi sarcoma (CKS). In population I, we examined FCGR3A variants and risk of KSHV infection in 34 KSHV latent nuclear antigen (LANA)-seropositive and 120 LANAseronegative adults from Sardinia (52% male; median age, 45 years; range, 31-60), whereas in population II, we examined risk of CKS from 133 CKS cases and 172 KSHV LANA-seropositive controls from Sicily, Rome, and Naples (70% males; median age, 74 years; range, 29-91). FCGR3A variants were determined by direct sequence analysis of a nested PCR of genomic DNA assay using allele-specific primers. KSHV LANA was determined by immunofluorescence assay. Overall, compared with the 158F allele, 158V was overrepresented among controls from both Mediterranean populations (frequency = 0.52 and 0.51, respectively). After controlling for age, 158V homozygous women were at increased risk of KSHV infection and CKS compared with 158F homozygous women [odds ratio (OR), 8.7; 95% confidence interval (95% CI), 0.8-98 and OR, 3.8; 95% CI, 1.0-14, respectively], whereas homozygous men were at decreased risk (OR, 0.4; 95% CI, 0.1-2.3 and OR, 0.4; 95% CI, 0.2-0.8, respectively). Significant gene-dose effects were observed among men and women at risk for CKS (P trend V V V 0.05). Our findings suggest that gender differences could possibly modify the effect of FCGR3A on risk of KSHV infection and CKS. Additional studies are required to confirm these relationships and determine their etiologic significance.

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“…Natural killer cells have been shown to target KSHV-infected cell lines and this activity is recovered in people with HIV and AIDS (PWHA) who resolve their KS lesions during antiretroviral therapy (22). However, the absolute numbers of NK cells do not appear to influence the relative risk of KS in PWHA, indicating that other factors control KSHV infection and the acquisition of KS lesions (23).…”

mentioning

confidence: 99%

NKG2C ⁺ NK Cells Are Enriched in AIDS Patients with Advanced-Stage Kaposi's Sarcoma

Goodier

Mela

Steel³

et al. 2007

J Virol

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Kaposi's sarcoma (KS) is an AIDS-defining condition in individuals withRecognition of infected target cells by NK cells is regulated by receptors for major histocompatibility complex class I (MHC-I) and pathogen-derived molecules (3,14). Killer cell immunoglobulin-like receptor (KIR) family members, which are expressed on NK cells, influence the risk of progression to AIDS in combination with HLA-B alleles (15, 16). However, the proportion of NK cells expressing inhibitory KIR increases and those expressing activating natural cytotoxicity receptors (NCR) are less abundant in PWHA (1,5,6,17).We have shown that NK cells from PWHA are enriched for a subset bearing the C-type, lectin-like receptor NKG2C (20). The NKG2C receptor mediates NK cell responses to a limited set of ligands in association with HLA-E, including a human cytomegalovirus (HCMV) peptide, and to HCMV-infected fibroblasts (9, 10). However, NK cells bearing NKG2C predominantly express inhibitory KIR and have low levels of activating NCR, which may compromise their abilities to mount cytolytic responses (8,20).As NKG2C ϩ NK cells have a predominantly inhibitory phenotype, the dominance of this subset could have an impact on disease prognosis in AIDS patients, including those with KS. We used the AIDS Clinical Trial Group (ACTG) clinical staging system, which is applied to all AIDS KS patients upon diagnosis, to investigate the relationship between the NK cell phenotype and function and disease prognosis in HIV-1 infection.Patients

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NK cell activity controls human herpesvirus 8 latent infection and is restored upon highly active antiretroviral therapy in AIDS patients with regressing Kaposi's sarcoma

Cited by 72 publications

References 37 publications

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

A Common Genetic Variant inFCGR3A-V158F and Risk of Kaposi Sarcoma Herpesvirus Infection and Classic Kaposi Sarcoma

NKG2C ⁺ NK Cells Are Enriched in AIDS Patients with Advanced-Stage Kaposi's Sarcoma

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NK cell activity controls human herpesvirus 8 latent infection and is restored upon highly active antiretroviral therapy in AIDS patients with regressing Kaposi's sarcoma

Cited by 72 publications

References 37 publications

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

A Common Genetic Variant inFCGR3A-V158F and Risk of Kaposi Sarcoma Herpesvirus Infection and Classic Kaposi Sarcoma

NKG2C + NK Cells Are Enriched in AIDS Patients with Advanced-Stage Kaposi's Sarcoma

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NKG2C ⁺ NK Cells Are Enriched in AIDS Patients with Advanced-Stage Kaposi's Sarcoma