Reactivation and Lytic Replication of Kaposi’s Sarcoma-Associated Herpesvirus: An Update

Aneja, Kawalpreet K.; Yuan, Yan

doi:10.3389/fmicb.2017.00613

Cited by 151 publications

(159 citation statements)

References 241 publications

(306 reference statements)

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“…Physiological triggers that induce gammaherpesvirus reactivation are not as clear as in the case of other herpesviruses (see below). Infections by other viruses, such as HIV, HSV-1, HSV-2, HHV-6, HHV-7, HCMV, and papillomavirus can contribute to lytic reactivation of KSHV [179][180][181][182]. Further research has shown that activation of Toll-like receptors 6 and 7 (TLR6 and TLR7) by other viruses can trigger KSHV reactivation [180].…”

Section: Virus Reactivationmentioning

confidence: 99%

Herpesviral Latency—Common Themes

2020

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Latency establishment is the hallmark feature of herpesviruses, a group of viruses, of which nine are known to infect humans. They have co-evolved alongside their hosts, and mastered manipulation of cellular pathways and tweaking various processes to their advantage. As a result, they are very well adapted to persistence. The members of the three subfamilies belonging to the family Herpesviridae differ with regard to cell tropism, target cells for the latent reservoir, and characteristics of the infection. The mechanisms governing the latent state also seem quite different. Our knowledge about latency is most complete for the gammaherpesviruses due to previously missing adequate latency models for the alpha and beta-herpesviruses. Nevertheless, with advances in cell biology and the availability of appropriate cell-culture and animal models, the common features of the latency in the different subfamilies began to emerge. Three criteria have been set forth to define latency and differentiate it from persistent or abortive infection: 1) persistence of the viral genome, 2) limited viral gene expression with no viral particle production, and 3) the ability to reactivate to a lytic cycle. This review discusses these criteria for each of the subfamilies and highlights the common strategies adopted by herpesviruses to establish latency.

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Section: Virus Reactivationmentioning

confidence: 99%

Herpesviral Latency—Common Themes

2020

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“…A classic example is herpes simplex virus-1 (HSV-1/HHV- 1) infection, which produces primary vesicular lesions in the oral mucosa and establishes latency in adjacent neural ganglia where reactivation of the virus leads to formation of repeated lesions in the same area over the course of the infected individual's life [4][5][6]. Other herpesviruses such as human cytomegalovirus (HCMV/HHV-5) and Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) establish latency in various myeloid and lymphoid compartments, often without symptoms associated with reactivation except in the cases of immunosuppression such as organ transplantation or untreated HIV-1 infection [7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

A Conserved Mechanism of APOBEC3 Relocalization by Herpesviral Ribonucleotide Reductase Large Subunits

Cheng

Moraes

Attarian

et al. 2019

J Virol

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An integral part of the antiviral innate immune response is the APOBEC3 family of single-stranded DNA cytosine deaminases, which inhibits virus replication through deamination-dependent and -independent activities. Viruses have evolved mechanisms to counteract these enzymes, such as HIV-1 Vif-mediated formation of a ubiquitin ligase to degrade virus-restrictive APOBEC3 enzymes. A new example is Epstein-Barr virus (EBV) ribonucleotide reductase (RNR)-mediated inhibition of cellular APOBEC3B (A3B). The large subunit of the viral RNR, BORF2, causes A3B relocalization from the nucleus to cytoplasmic bodies and thereby protects viral DNA during lytic replication. Here, we use coimmunoprecipitation and immunofluorescence microscopy approaches to ask whether this mechanism is shared with the closely related gammaherpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV) and the more distantly related alphaherpesvirus herpes simplex virus 1 (HSV-1). The large RNR subunit of KSHV, open reading frame 61 (ORF61), coprecipitated multiple APOBEC3s, including A3B and APOBEC3A (A3A). KSHV ORF61 also caused relocalization of these two enzymes to perinuclear bodies (A3B) and to oblong cytoplasmic structures (A3A). The large RNR subunit of HSV-1, ICP6, also coprecipitated A3B and A3A and was sufficient to promote the relocalization of these enzymes from nuclear to cytoplasmic compartments. HSV-1 infection caused similar relocalization phenotypes that required ICP6. However, unlike the infectivity defects previously reported for BORF2-null EBV, ICP6 mutant HSV-1 showed normal growth rates and plaque phenotypes. Combined, these results indicate that both gamma- and alphaherpesviruses use a conserved RNR-dependent mechanism to relocalize A3B and A3A and furthermore suggest that HSV-1 possesses at least one additional mechanism to neutralize these antiviral enzymes. IMPORTANCE The APOBEC3 family of DNA cytosine deaminases constitutes a vital innate immune defense against a range of different viruses. A novel counterrestriction mechanism has recently been uncovered for the gammaherpesvirus EBV, in which a subunit of the viral protein known to produce DNA building blocks (ribonucleotide reductase) causes A3B to relocalize from the nucleus to the cytosol. Here, we extend these observations with A3B to include a closely related gammaherpesvirus, KSHV, and a more distantly related alphaherpesvirus, HSV-1. These different viral ribonucleotide reductases also caused relocalization of A3A, which is 92% identical to A3B. These studies are important because they suggest a conserved mechanism of APOBEC3 evasion by large double-stranded DNA herpesviruses. Strategies to block this host-pathogen interaction may be effective for treating infections caused by these herpesviruses.

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“…Importantly, tumors associated with KSHV infection mostly present with viruses in a latent state; this observation led to the consideration of lytic reactivation not involved in tumorigenesis. Actually, it is recently emerging that both latency and lytic reactivation play a key role in KSHV-induced carcinogenesis (Aneja and Yuan, 2017). To this regard, it has been characterized that latent infection promotes proliferation and cell survival (Cesarman et al, 2019); by counterpart, virus reactivation not only ensures a higher dissemination of viral particles but also promotes angiogenesis (Asou et al, 1998;Wu et al, 2014) and the evasion of immunoresponse (Zhao et al, 2015), promoting cancer development.…”

Section: Kaposi's Sarcoma-associated Herpesvirus (Kshv)mentioning

confidence: 99%

Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development

Vescovo

Pagni

Piacentini

et al. 2020

Front. Cell Dev. Biol.

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About 20% of total cancer cases are associated to infections. To date, seven human viruses have been directly linked to cancer development: high-risk human papillomaviruses (hrHPVs), Merkel cell polyomavirus (MCPyV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human T-lymphotropic virus 1 (HTLV-1). These viruses impact on several molecular mechanisms in the host cells, often resulting in chronic inflammation, uncontrolled proliferation, and cell death inhibition, and mechanisms, which favor viral life cycle but may indirectly promote tumorigenesis. Recently, the ability of oncogenic viruses to alter autophagy, a catabolic process activated during the innate immune response to infections, is emerging as a key event for the onset of human cancers. Here, we summarize the current understanding of the molecular mechanisms by which human oncogenic viruses regulate autophagy and how this negative regulation impacts on cancer development. Finally, we highlight novel autophagy-related candidates for the treatment of virus-related cancers. Keywords: oncogenic (or carcinogenic) viruses, autopaghy, human papillomavirus (HPV), Merkel cell polyomavirus (MCPyV), hepatitis B and C viruses (HBV and HCV), Epstein-Barr virus (EBV), Kaposi's sarcomaassociated herpesvirus (KSHV), human T-lymphotropic virus 1 (HTLV-1)

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Reactivation and Lytic Replication of Kaposi’s Sarcoma-Associated Herpesvirus: An Update

Cited by 151 publications

References 241 publications

Herpesviral Latency—Common Themes

Herpesviral Latency—Common Themes

A Conserved Mechanism of APOBEC3 Relocalization by Herpesviral Ribonucleotide Reductase Large Subunits

Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development

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