Dataset Information

Detection and analysis of variants of JC polyomavirus in urine samples from HIV-1-infected patients in China's Zhejiang Province.

ABSTRACT: Objectives Human JC polyomavirus (JCPyV) infection has an increased risk of developing progressive multifocal leukoencephalopathy (PML). Different JCPyV subtypes differ in the virulence with which they cause PML. Currently, the JCPyV infection status and subtype distribution in patients with human immunodeficiency virus-1 (HIV-1) in China are still unclear. This study aimed to investigate the epidemiology and subtype distribution of JCPyV in HIV-1-infected patients in China. Methods Urine samples from 137 HIV-1-infected patients in Zhejiang Province in China were tested for the presence of JCPyV DNA. The detected VP1 sequences were aligned and analysed using BioEdit and MEGA software. Results Among urine samples from HIV-1-infected patients, 67.2% were positive for JCPyV DNA (92/137). Primarily, the type 7 strains of JCPyV were detected, among which 45.5% (15/33) were subtype 7A, 30.3% (10/33) were 7B, and 24.2% (8/33) were 7C. Six nucleotide mutations, as well as one amino acid substitution, were isolated from the patients. Conclusions Urine samples from HIV-1-infected patients from Zhejiang Province show a high JCPyV infection rate. The most common JCPyV strains are subtypes 7A, 7B, and 7C.

SUBMITTER: Hu C

PROVIDER: S-EPMC5972266 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Detection and analysis of variants of JC polyomavirus in urine samples from HIV-1-infected patients in China's Zhejiang Province.

Hu Caiqin C Huang Ying Y Su Junwei J Wang Mengyan M Zhou Qihui Q Zhu Biao B

The Journal of international medical research 20180111 3

Objectives Human JC polyomavirus (JCPyV) infection has an increased risk of developing progressive multifocal leukoencephalopathy (PML). Different JCPyV subtypes differ in the virulence with which they cause PML. Currently, the JCPyV infection status and subtype distribution in patients with human immunodeficiency virus-1 (HIV-1) in China are still unclear. This study aimed to investigate the epidemiology and subtype distribution of JCPyV in HIV-1-infected patients in China. Methods Urine sample ...[more]

PMID: 29322824

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Project description:Defective viral genomes (DVGs) are parasitic viral sequences containing point mutations, deletions, or duplications that might interfere with replication. DVGs are often associated with viral passage at high multiplicities of infection in culture systems but have been increasingly reported in clinical specimens. To date however, only RNA viruses have been shown to contain DVGs in clinical specimens. Here, using direct deep sequencing with multiple library preparation strategies and confirmatory digital droplet PCR (ddPCR) of urine samples taken from immunosuppressed individuals, we show that clinical BK polyomavirus (BKPyV) and JC polyomavirus (JCPyV) strains contain widespread genomic rearrangements across multiple loci that likely interfere with viral replication. BKPyV DVGs were derived from BKPyV genotypes Ia, Ib-1, and Ic. The presence of DVGs was associated with specimens containing higher viral loads but never reached clonality, consistent with a model of parasitized replication. These DVGs persisted during clinical infection as evidenced in two separate pairs of samples containing BK virus collected from the same individual up to 302 days apart. In a separate individual, we observed the generation of DVGs after a 57.5-fold increase in viral load. In summary, by extending the presence of DVGs in clinical specimens to DNA viruses, we demonstrate the ubiquity of DVGs in clinical virology.IMPORTANCE Defective viral genomes (DVGs) can have a significant impact on the production of infectious virus particles. DVGs have only been identified in cultured viruses passaged at high multiplicities of infection and RNA viruses collected from clinical specimens; no DNA virus in the wild has been shown to contain DVGs. Here, we identified BK and JC polyomavirus DVGs in clinical urine specimens and demonstrated that these DVGs are more frequently identified in samples with higher viral loads. The strains containing DVGs had rearrangements throughout their genomes, with the majority affecting genes required for viral replication. Longitudinal analysis showed that these DVGs can persist during an infection but do not reach clonality within the chronically infected host. Our identification of polyomavirus DVGs suggests that these parasitic sequences exist across the many classes of viruses capable of causing human disease.

Project description:JC polyomavirus (JCV) carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML) which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50-60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA), instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP) kits and a reverse PCR sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR?=?0.42, p?=?7×10(-15)) and controls (OR?=?0.53, p?=?2×10(-5)). In contrast, the DQB1*06:03 haplotype was positively associated with JCV sero-status, in Scandinavian MS cases (OR?=?1.63, p?=?0.006), and controls (OR?=?2.69, p?=?1×10(-5)). The German dataset confirmed these findings (OR?=?0.54, p?=?1×10(-4) and OR?=?1.58, p?=?0.03 respectively for these haplotypes). HLA class II restricted immune responses, and hence CD4+ T cell immunity is pivotal for JCV infection control. Alleles within the HLA-DR1*15 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB1*06:03 haplotype show an opposite association. These associations between JC virus antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and lays the ground for risk stratification for PML and development of therapy and prevention.

Dataset Information

Detection and analysis of variants of JC polyomavirus in urine samples from HIV-1-infected patients in China's Zhejiang Province.

Publications

Detection and analysis of variants of JC polyomavirus in urine samples from HIV-1-infected patients in China's Zhejiang Province.

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