JC Virus Propagation is Potentiated by Glial Replication and Accelerated by Demyelination-Associated Glial Proliferation

ABSTRACT Virus-encoded capsid proteins play a major role in the life cycles of all viruses. The JC virus capsid is composed of 72 pentamers of the major capsid protein Vp1, with one of the minor coat proteins Vp2 or Vp3 in the center of each pentamer. Vp3 is identical to two-thirds of Vp2, and these proteins share a DNA binding domain, a nuclear localization signal, and a Vp1-interacting domain. We demonstrate here that both the minor proteins and the myristylation site on Vp2 are essential for the viral life cycle, including the proper packaging of its genome.

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A Prospective Study Demonstrates an Association Between JC Virus-Specific Cytotoxic T Lymphocytes and the Early Control of Progressive Multifocal Leukoencephalopathy

Yearbook of Neurology and Neurosurgery ◽

10.1016/s0513-5117(08)70276-x ◽

2006 ◽

Vol 2006 ◽

pp. 65-66

Author(s):

J.R. Berger

Keyword(s):

T Lymphocytes ◽

Progressive Multifocal Leukoencephalopathy ◽

Prospective Study ◽

Cytotoxic T Lymphocytes ◽

Jc Virus ◽

A Prospective Study

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JC Virus spezifische microRNA als Stuhl-Biomarker für Patienten mit kolorektalen Neoplasien

Zeitschrift für Gastroenterologie ◽

10.1055/s-0031-1285390 ◽

2011 ◽

Vol 49 (08) ◽

Author(s):

A Link ◽

F Balaguer ◽

Y Shen ◽

CR Boland ◽

A Goel

Keyword(s):

Jc Virus

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Analysis of JC virus DNA purified directly from human progressive multifocal leukoencephalopathy brains.

Journal of Virology ◽

10.1128/jvi.38.2.761-769.1981 ◽

1981 ◽

Vol 38 (2) ◽

pp. 761-769 ◽

Cited By ~ 19

Author(s):

F Rentier-Delrue ◽

A Lubiniecki ◽

P M Howley

Keyword(s):

Progressive Multifocal Leukoencephalopathy ◽

Jc Virus

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Sequence rearrangement in JC virus DNAs molecularly cloned from immunosuppressed renal transplant patients.

Journal of Virology ◽

10.1128/jvi.65.5.2422-2428.1991 ◽

1991 ◽

Vol 65 (5) ◽

pp. 2422-2428 ◽

Cited By ~ 45

Author(s):

Y Yogo ◽

T Kitamura ◽

C Sugimoto ◽

K Hara ◽

T Iida ◽

...

Keyword(s):

Renal Transplant ◽

Jc Virus ◽

Transplant Patients ◽

Sequence Rearrangement ◽

Renal Transplant Patients

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Discriminating between JCPyV and BKPyV in Urinary Virome Data Sets

Viruses ◽

10.3390/v13061041 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1041

Author(s):

Rita Mormando ◽

Alan J. Wolfe ◽

Catherine Putonti

Keyword(s):

Jc Virus ◽

Sequence Similarity ◽

Bk Virus ◽

Data Sets ◽

Metagenomic Sequencing ◽

Significant Sequence Similarity ◽

Sequence Identity ◽

Shotgun Metagenomic Sequencing ◽

Urinary Microbiome ◽

Six Genes

Polyomaviruses are abundant in the human body. The polyomaviruses JC virus (JCPyV) and BK virus (BKPyV) are common viruses in the human urinary tract. Prior studies have estimated that JCPyV infects between 20 and 80% of adults and that BKPyV infects between 65 and 90% of individuals by age 10. However, these two viruses encode for the same six genes and share 75% nucleotide sequence identity across their genomes. While prior urinary virome studies have repeatedly reported the presence of JCPyV, we were interested in seeing how JCPyV prevalence compares to BKPyV. We retrieved all publicly available shotgun metagenomic sequencing reads from urinary microbiome and virome studies (n = 165). While one third of the data sets produced hits to JCPyV, upon further investigation were we able to determine that the majority of these were in fact BKPyV. This distinction was made by specifically mining for JCPyV and BKPyV and considering uniform coverage across the genome. This approach provides confidence in taxon calls, even between closely related viruses with significant sequence similarity.

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IKKε isoform switching governs the immune response against EV71 infection

Communications Biology ◽

10.1038/s42003-021-02187-x ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Ya-Ling Chang ◽

Yu-Wen Liao ◽

Min-Hsuan Chen ◽

Sui-Yuan Chang ◽

Yao-Ting Huang ◽

...

Keyword(s):

Host Cells ◽

Ev71 Infection ◽

Virus Propagation ◽

Host Interactions ◽

Reciprocal Interactions ◽

Isoform Switching ◽

Gene Regulatory ◽

Potential Strategy ◽

Antiviral Innate Immunity ◽

Interferon Responses

AbstractThe reciprocal interactions between pathogens and hosts are complicated and profound. A comprehensive understanding of these interactions is essential for developing effective therapies against infectious diseases. Interferon responses induced upon virus infection are critical for establishing host antiviral innate immunity. Here, we provide a molecular mechanism wherein isoform switching of the host IKKε gene, an interferon-associated molecule, leads to alterations in IFN production during EV71 infection. We found that IKKε isoform 2 (IKKε v2) is upregulated while IKKε v1 is downregulated in EV71 infection. IKKε v2 interacts with IRF7 and promotes IRF7 activation through phosphorylation and translocation of IRF7 in the presence of ubiquitin, by which the expression of IFNβ and ISGs is elicited and virus propagation is attenuated. We also identified that IKKε v2 is activated via K63-linked ubiquitination. Our results suggest that host cells induce IKKε isoform switching and result in IFN production against EV71 infection. This finding highlights a gene regulatory mechanism in pathogen-host interactions and provides a potential strategy for establishing host first-line defense against pathogens.

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JC Virus Seroprevalence and JCVAb Index in Polish Multiple Sclerosis Patients Treated with Immunomodulating or Immunosuppressive Therapies

Journal of Clinical Medicine ◽

10.3390/jcm10091998 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1998

Author(s):

Robert Bonek ◽

Wojciech Guenter ◽

Robert Jałowiński ◽

Anna Karbicka ◽

Anna Litwin ◽

...

Keyword(s):

Multiple Sclerosis ◽

Jc Virus ◽

Dimethyl Fumarate ◽

Risk Category ◽

Seroprevalence Rate ◽

Immunomodulatory Drugs ◽

Cross Sectional ◽

Treatment Type ◽

Multiple Sclerosis Patients ◽

The Impact

The use of a highly-effective treatment for multiple sclerosis (MS) is associated with a severe risk of developing complications, such as progressive multifocal leukoencephalopathy (PML) caused by the John Cunningham virus (JCV). The aim of this study was to evaluate the correlation between anti-JCV Ab seroprevalence, anti-JCV AI, demographic and clinical factors as well as the type of therapy used in the Polish MS population. This is a multicentre, prospective and cross-sectional study involving 1405 MS patients. The seroprevalence of anti-JCV Ab and anti-JCV AI levels as well as AI categories were analysed with the use of a second-generation two-step ELISA test (STRATIFY JCV DxSelect). The overall prevalence of anti-JCV Ab was 65.8%. It was shown that seroprevalence increases with the patient’s age. The seroprevalence was significantly associated with the treatment type, and the highest values (76%) were obtained from immunosuppressant-treated patients. Overall, 63.3% of seropositive patients had an antibody index (AI) level of >1.5. In the seropositive patient group, the mean AI level amounted to 2.09. Similarly to the seroprevalence, AI levels correlated with the patient’s age; AI level for patients above 40 years old and from subsequent age quintiles plateaued, amounting to at least 1.55. Patients treated with immunosuppressants and immunomodulatory drugs obtained the highest (1.67) and lowest (1.35) AI levels, respectively. Of the immunosuppressants used, the highest mean AI levels were observed in mitoxantrone and cladribine groups, amounting to 1.75 and 1.69, respectively. In patients treated with immunomodulatory drugs, the lowest AI levels were observed in the dimethyl fumarate (DMF) group (1.11). The seroprevalence rate in the Polish MS population is one of the highest in Europe. The majority of seropositive patients had an anti-JCV Ab level qualifying them for a high-risk category. The highest mean AI levels are observed in patients receiving immunosuppressants, especially mitoxantrone and cladribine. Patients receiving immunomodulatory drugs have lower AI levels compared to treatment-naïve subjects, especially when treated with DMF. Further studies, especially longitudinal studies, are required to determine the impact of MS drugs on the seroprevalence of anti-JCV Ab and AI levels.

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