Novel Organizational Features, Captured Cellular Genes, and Strain Variability Within the Genome of KSHV/HHV8

Nicholas, John; Zong, Jianchao; Alcendor, Donald J.; Ciufo, Dolores M.; Poole, Lynn; Sarisky, Robert T.; Chiou, Chuang-Jiun; Zhang, Xiaoqun; Wan, Xiao; Guo, Hongyu; Reitz, Marvin S.; Hayward, Gary S.

doi:10.1093/oxfordjournals.jncimonographs.a024179

Cited by 127 publications

(93 citation statements)

References 44 publications

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“…Genes that are found only in other rhadinoviruses and those that are unique to HHV-8 are encoded within 'nonconserved' gene blocks in the viral genome (Neipel et al, 1997). These genes include several growth factor homologues, for example, viral IL-6 (ORFK2), two macrophage inflammatory protein (MIP)-1a homologues (ORFK4, ORFK6), and one MIP-1b homologue (ORFK4.1) (Nicholas et al, 1997a(Nicholas et al, , b, 1998. Like HVS, HHV-8 encodes a type-D cyclin (ORF72) that affects cell-cycle regulation, and a vBcl-2 (ORF16) that may contribute to preventing Bax-mediated apoptosis (Neipel et al, 1997).…”

Section: Genomic Organization and Gene Expression Pattern Of Hhv-8mentioning

confidence: 99%

The role of Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 regulator of transcription activation (RTA) in control of gene expression

2003

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The mechanisms that control the replication state, latency versus lytic, of human herpesviruses have been under intense investigations. Here we summarize some of the recent findings that help define such mechanisms for Kaposi's sarcoma-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV-8). For HHV-8, the viral regulator of transcription activation (RTA) is a key mediator of the switch from latency to lytic gene expression in infected cells. RTA is necessary and sufficient to drive HHV-8 lytic replication and the production of viral progeny. The RTA is an immediateearly gene product, it is the initial activator of expression of a multitude of viral and cellular genes that have been implicated in the replication of HHV-8 and pathogenesis of KS. Interactions of RTA with a number of viral promoters, and with a number of transcription factors or transcriptional co-activators are highlighted. Modulation of transactivation, through alternate RTA-protein, or RTA-promoter interactions, is hypothesisized to participate in the selective tissue tropism and differential pathogenesis observed in KS.

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Section: Genomic Organization and Gene Expression Pattern Of Hhv-8mentioning

confidence: 99%

The role of Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 regulator of transcription activation (RTA) in control of gene expression

2003

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“…There is substantial K1 genetic diversity in circulating KSHV strains (Biggar et al, 2000;Cook et al, 1999;Meng et al, 1999;Zong et al, 1999). Among KSHV subtypes A, B, C, D and E, there is a 15-30% amino acid difference overall and a 30-60% amino acid difference within two K1 variable regions, VR1 and VR2 (Nicholas et al, 1998;Zong et al, 1999;Biggar et al, 2000). The high rate of nonsynonymous to synonymous substitution in K1 suggests that K1 is undergoing positive biological selection and could be an important virulence factor and/or target of the host immune system (Cook et al, 1999;Hayward, 1999;McGeoch and Davidson, 1999).…”

Section: Introductionmentioning

confidence: 99%

Genetic diversity of the Kaposi's sarcoma herpesvirus K1 protein in AIDS-KS in Zimbabwe

White¹,

Hagen²,

Gudza³

et al. 2008

Journal of Clinical Virology

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“…The ORF-K1 gene has since been identified as the area with the highest sequence variability [Nicholas et al, 1998]. So far four subtypes (A, B, C, and D) and at least 13 distinct variants were identified on the basis of sequence heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

HHV‐8 subtypes in South Africa: Identification of a case suggesting a novel B variant

Treurnicht

Engelbrecht

Taylor

et al. 2001

Journal of Medical Virology

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Human herpesvirus 8 (HHV-8) has been identified as the causative agent for all forms of Kaposi's sarcoma and is also associated with the development of body cavity-based B-cell lymphomas and multicentric Castleman's disease. HHV-8 genomes are now classified into five major subtypes (A-E) that reflect sequence heterogeneity in the highly variable open reading frame (ORF) K1. To identify HHV-8 subtypes associated with different forms of Kaposi's sarcoma, we compared the ORF 26 and ORF-K1 gene sequences from South African patients with the prototype strains of the major subtypes, as well as published sequences from other African strains. DNA prepared from Kaposi's sarcoma biopsies and/or peripheral blood lymphocytes were available from 14 patients with postrenal transplant (iatrogenic) Kaposi's sarcoma, six patients with the African endemic form, and one patient with AIDS-related body cavity-based B-cell lymphoma. We identified a B2 subtype in six patients, four of whom also had a novel B5 type ORF 26 polymorphism. Two patients had B2 type patterns for both the ORF 26 and ORF-K1 genes. The ORF-K1 subtype A5 was identified in samples from three patients with a B3/C2 type polymorphism in the ORF 26 gene. A novel ORF-K1 B variant strain was identified in a patient with African endemic Kaposi's sarcoma, who also had a B3/C2 class ORF 26 pattern. In 58.3% of iatrogenic Kaposi's sarcoma patients, a B5-type ORF 26 gene sequence pattern was identified. No association was found among particular subtypes, geographical origin of patients, or clinical presentation.

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Novel Organizational Features, Captured Cellular Genes, and Strain Variability Within the Genome of KSHV/HHV8

Cited by 127 publications

References 44 publications

The role of Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 regulator of transcription activation (RTA) in control of gene expression

The role of Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 regulator of transcription activation (RTA) in control of gene expression

Genetic diversity of the Kaposi's sarcoma herpesvirus K1 protein in AIDS-KS in Zimbabwe

HHV‐8 subtypes in South Africa: Identification of a case suggesting a novel B variant

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