Kaposi’s Sarcoma-Associated Herpesvirus Subversion of the Anti-Inflammatory Response in Human Skin Cells Reveals Correlates of Latency and Disease Pathogenesis

Fontana, John L.; Mygatt, Justin G.; Conant, Katelyn L.; Parsons, Chris; Kaleeba, Johnan A.R.

doi:10.1155/2014/246076

Cited by 4 publications

(2 citation statements)

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“…In cell culture, KSHV is able to infect various types of human cells, such as B cells, endothelial cells, epithelial cells, and fibroblasts (Dai et al, 2012; Fontana et al, 2014; Kang and Myoung, 2017). Several membrane proteins including heparin sulfate proteoglycan (HSPG), DC-SIGN, integrin α3β1/αvβ3, EphA2 and xCT can act as cellular receptors for KSHV infection in a cell type-dependent manner (Birkmann et al, 2001; Akula et al, 2002; Kaleeba and Berger, 2006; Rappocciolo et al, 2006; Garrigues et al, 2008; Hahn et al, 2012).…”

Section: Role Of Lipids In the Primary And Latent Kshv Infectionmentioning

confidence: 99%

Lipids, lipid metabolism and Kaposi’s sarcoma-associated herpesvirus pathogenesis

et al. 2017

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Lipids are essential for mammalian cells to maintain many physiological functions. Emerging evidence has shown that cancer cells can develop specific alterations in lipid biosynthesis and metabolism to facilitate their survival and various malignant behaviors. To date, the precise role of cellular lipids and lipid metabolism in viral oncogenesis is still largely unclear with only a handful of literature covering this topic to implicate lipid metabolism in oncogenic virus associated pathogenesis. In this review, we focus on the role of lipid biosynthesis and metabolism in the pathogenesis of the Kaposi’s sarcoma-associated herpesvirus, a common causative factor for cancers arising in the immunocompromised settings.

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Section: Role Of Lipids In the Primary And Latent Kshv Infectionmentioning

confidence: 99%

Lipids, lipid metabolism and Kaposi’s sarcoma-associated herpesvirus pathogenesis

et al. 2017

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“…In a healthy population, there is great variability in the seroprevalence of HHV-8, as opposed to groups at increased risk of developing KS. HHV-8 undergoes both latent and lytic phases in its life cycle, whereby the virus remains within the host at a dormant stage until other cofactors trigger it to start replicating, leading to the lytic phase [ 7 , 8 , 9 ]. The mode of transmission of HHV-8 can either be vertical or horizontal, including mother to child transmission and from members of family units [ 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

HHV-8 Seroprevalence and Genotype Distribution in Africa, 1998–2017: A Systematic Review

Etta

Alayande

Mavhandu-Ramarumo

et al. 2018

Viruses

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Human herpes virus type 8 (HHV-8) is the causative agent of Kaposi’s sarcoma (KS). We systematically reviewed literature published between 1998 and 2017, according to the PRISMA guidelines, to understand the distribution of HHV-8 infection in Africa. More than two-thirds (64%) of studies reported on seroprevalence and 29.3% on genotypes; 9.5% were on both seroprevalence and genotypes. About 45% of African countries had data on HHV-8 seroprevalence exclusively, and more than half (53%) had data on either seroprevalence or genotypes. Almost half (47%) of the countries had no data on HHV-8 infection. There was high heterogeneity in the types of tests and interpretation algorithms used in determining HHV-8 seropositivity across the different studies. Generally, seroprevalence ranged from 2.0% in a group of young children in Eritrea to 100% in a small group of individuals with KS in Central African Republic, and in a larger group of individuals with KS in Morocco. Approximately 16% of studies reported on children. Difference in seroprevalence across the African regions was not significant (95% CI, χ2 = 0.86; p = 0.35), although specifically a relatively significant level of infection was observed in HIV-infected children. About 38% of the countries had data on K1 genotypes. K1 genotypes A, A5, B, C, F and Z occurred at frequencies of 5.3%, 26.3%, 42.1%, 18.4%, 5.3% and 2.6%, respectively. Twenty-three percent of the countries had data for K15 genotypes, and genotypes P, M and N occurred at frequencies of 52.2%, 39.1%, and 8.7%, respectively. Data on HHV-8 inter-genotype recombinants in Africa are scanty. HHV-8 may be endemic in the entire Africa continent but there is need for a harmonized testing protocol for a better understanding of HHV-8 seropositivity. K1 genotypes A5 and B, and K15 genotypes P and M, from Africa, should be considered in vaccine design efforts.

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Altering the Anti-inflammatory Lipoxin Microenvironment: a New Insight into Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis

Chandrasekharan¹,

Huang

Hwang

et al. 2016

J Virol

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Lipoxins are host anti-inflammatory molecules that play a vital role in restoring tissue homeostasis. The efficacy of lipoxins and their analog epilipoxins in treating inflammation and its associated diseases has been well documented. Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL) are two well-known inflammation related diseases caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Controlling inflammation is one of the strategies adopted to treat KS and PEL, a primary motivation for exploring and evaluating the therapeutic potential of using lipoxins. This study documents how KSHV manipulates and downregulates the secretion of the anti-inflammatory lipoxin A4 in host cells and the viral factors involved in this process using Kaposi's sarcoma-associated herpesvirus (KSHV), also termed human herpesvirus 8 (HHV-8), is etiologically associated with Kaposi's sarcoma (KS) and B-cell lymphoproliferative primary effusion lymphoma (PEL). KS is a proliferative angiogenic tumor of endothelial cells characterized by vascular red/purplish lesions in the skin (1-3). PEL, also known as body cavity lymphoma, is a non-Hodgkin's lymphoma primarily present in the body cavity (4). KS and PEL are a significant cause of death in HIV patients. The presence of a suppressed host immune system along with KSHV-coded immunomodulatory proteins contributes to KSHV infection, and the lifelong KSHV latency establishment is the primary factor for pathogenesis (5, 6). KSHV utilizes its latency cluster containing ORF73 (latency-associated nuclear antigen 1 [LANA-1]), ORF72 (viral cyclin [vCyclin]), ORF71 (K13/ vFLIP), and ORFK12 (kaposins A, B, and C), as well as 12 distinct pre-microRNAs, to modulate the host immune system and maintain lifelong latency (7-9). KSHV also encodes several homologs of cytokines and chemokines to alter the immune response (6).KSHV induces several proinflammatory host molecules such as COX-2/PGE2, 5-lipoxygenase, and LTB4 to establish latency and aid in its pathogenesis (10)(11)(12)(13)(14). Beside upregulating proinflammatory pathways, KSHV also modulates the immune system by downregulating anti-inflammatory pathways (15). Since altering the host immune system is the hallmark of KSHV infection and pathogenesis, it is important to understand the relationship between the various components of the host immune system and KSHV to design better therapeutics.To date, there is no effective treatment for KS and PEL. Current treatment involves the use of chemotherapeutics that work by targeting DNA replication of all dividing cells. This approach has the following disadvantages: low efficacy, cytotoxic side effects, depletion of CD4, and risk of secondary malignancies. Above all, these anticancer drugs do not control viral replication and pathogenesis. Surgery is an expensive alternative effective for small size lesions the chance of disease relapse is high. Since KSHV in KS and PEL remains primarily in the latent form, antiviral drugs are not

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Kaposi’s Sarcoma-Associated Herpesvirus Subversion of the Anti-Inflammatory Response in Human Skin Cells Reveals Correlates of Latency and Disease Pathogenesis

Cited by 4 publications

References 81 publications

Lipids, lipid metabolism and Kaposi’s sarcoma-associated herpesvirus pathogenesis

Lipids, lipid metabolism and Kaposi’s sarcoma-associated herpesvirus pathogenesis

HHV-8 Seroprevalence and Genotype Distribution in Africa, 1998–2017: A Systematic Review

Altering the Anti-inflammatory Lipoxin Microenvironment: a New Insight into Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis

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