Asymptomatic Primary Merkel Cell Polyomavirus Infection among Adults

Tolstov, Yanis

doi:10.3201/eid1708.110079

Cited by 90 publications

(64 citation statements)

References 39 publications

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“…Except age, no other statistically significant associations have been consistently identified for MCPyV [13]. And till now, no definite transmission route for this virus has been demonstrated.…”

Section: Discussionmentioning

confidence: 92%

Seroprevalence of Merkel Cell Polyomavirus in the General Rural Population of Anyang, China

Zhang

Liu

et al. 2014

PLoS ONE

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BackgroundDespite the probably causal link between Merkel cell polyomavirus (MCPyV) infection and Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy, little is known about the seroepidemiology of MCPyV among healthy adults in China.MethodsSerum antibodies against MCPyV were evaluated by multiplex serology in a population-based study of 5548 adults (including 1587 heterosexual couples) aged 25–65 years who were enrolled from rural Anyang, China in 2007–2009. Univariate and multivariate logistic regression analyses were performed to assess the risk factors for the seropositivity of MCPyV.ResultsThe seroprevalence for MCPyV was 61.0%. MCPyV seropositivity was significantly higher in males than in females (64.5% vs. 57.7%, P<0.001), and for both genders, showed a trend of increase with age (Male: P trend<0.001; Female: P trend<0.001). Furthermore, among antibody positives, antibody levels of MCPyV increased with advancing age (P trend = 0.017). MCPyV seropositivity of one spouse was significantly associated with that of the other partner (Adjusted OR = 1.32, 95% CI: 1.07–1.62). However, there was no association between sexual behaviors and the seropositivity of MCPyV.ConclusionsHigh seroprevalence of MCPyV was observed in healthy Chinese individuals. Serological evidence suggests that nonsexual horizontal spread of MCPyV can occur among family members, and further research in this regard is needed.

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Section: Discussionmentioning

confidence: 92%

Seroprevalence of Merkel Cell Polyomavirus in the General Rural Population of Anyang, China

Zhang

Liu

et al. 2014

PLoS ONE

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“…Tumor surveys reveal high level MCV T antigen expression present only in MCC tumor specimens[90] (Figure 4C). Non-quantitative PCR frequently detects low level viral genome in non-cancerous tissues, consistent with MCV being a component of our healthy viral flora[102], and cannot be used to reliably distinguish cancer-associated from cancer-unassociated virus. Thus, specificity cannot be addressed by a dichotomous present/absent test for the virus but also should take into consideration high copy number vs. low copy number infections.…”

Section: MCV Over the Hill?mentioning

confidence: 99%

The conundrum of causality in tumor virology: The cases of KSHV and MCV

Moore

Chang

2014

Seminars in Cancer Biology

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Controversy has plagued tumor virology since the first tumor viruses were described over 100 years ago. Methods to establish cancer causation, such as Koch’s postulates, work poorly or not at all for these viruses. Kaposi’s sarcoma herpesvirus (KSHV/HHV8) and Merkel cell polyomavirus (MCV) were both found using nucleic acid identification methods but they represent opposite poles in the patterns for tumor virus epidemiology. KSHV is uncommon and has specific risk factors that contribute to infection and subsequent cancers. MCV and Merkel cell carcinoma (MCC), in contrast, is an example in which mutations to our normal viral flora contribute to cancer. Given the near-ubiquity of human MCV infection, establishing cancer causality relies on molecular evidence that does not fit comfortably within traditional infectious disease epidemiological models. These two viruses reveal some of the challenges and opportunities for inferring viral cancer causation in the age of molecular biology.

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“…Although production of a small amount of virus in persistently infected individuals has not been ruled out, the absence of a viral cytopathic effect and the limited ability to detect infectious virus in infected individuals suggest that MCV persistence largely reflects a true latent state. In support of this idea, MCV infection persists throughout the lifespan, and yet even under conditions of severe immune suppression, no disease syndrome has been described for actively replicating virus (16). In addition, transfection of plasmid viral DNA in cell culture produces scant viral particles even though the viral genome is maintained (15,17,18).…”

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confidence: 90%

Protein-mediated viral latency is a novel mechanism for Merkel cell polyomavirus persistence

Kwun

Chang

2017

Proc. Natl. Acad. Sci. U.S.A.

110

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Viral latency, in which a virus genome does not replicate independently of the host cell genome and produces no infectious particles, is required for long-term virus persistence. There is no known latency mechanism for chronic small DNA virus infections. Merkel cell polyomavirus (MCV) causes an aggressive skin cancer after prolonged infection and requires an active large T (LT) phosphoprotein helicase to replicate. We show that evolutionarily conserved MCV LT phosphorylation sites are constitutively recognized by cellular Fbw7, βTrCP, and Skp2 Skp-F-box-cullin (SCF) E3 ubiquitin ligases, which degrade and suppress steady-state LT protein levels. Knockdown of each of these E3 ligases enhances LT stability and promotes MCV genome replication. Mutations at two of these phosphoreceptor sites [serine (S)220 and S239] in the full viral genome increase LT levels and promote MCV virion production and transmission, which can be neutralized with anti-capsid antibody. Virus activation is not mediated by viral gene transactivation, given that these mutations do not increase late gene transcription in the absence of genome replication. Mechanistic target of rapamycin inhibition by either nutrient starvation or use of an active site inhibitor reduces Skp2 levels and stabilizes LT, leading to enhanced MCV replication and transmission. MCV can sense stresses in its intracellular environment, such as nutrient loss, through SCF E3 ligase activities, and responds by initiating active viral transmission. Protein-mediated viral latency through cellular SCF E3 ligase targeting of viral replication proteins is a unique form of latency that may promote chronic viral persistence for some small DNA and RNA viruses.Merkel cell polyomavirus | large T | latency | E3 ligase | transmission

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Asymptomatic Primary Merkel Cell Polyomavirus Infection among Adults

Abstract: TOC Summary: This virus may be part of normal human flora and harmless in most adults.

Cited by 90 publications

References 39 publications

Seroprevalence of Merkel Cell Polyomavirus in the General Rural Population of Anyang, China

Seroprevalence of Merkel Cell Polyomavirus in the General Rural Population of Anyang, China

The conundrum of causality in tumor virology: The cases of KSHV and MCV

Protein-mediated viral latency is a novel mechanism for Merkel cell polyomavirus persistence

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