Discovery of a Novel Polyomavirus in Acute Diarrheal Samples from Children

Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America
PLoS ONE (Impact Factor: 3.53). 11/2012; 7(11):e49449. DOI: 10.1371/journal.pone.0049449
Source: PubMed

ABSTRACT Polyomaviruses are small circular DNA viruses associated with chronic infections and tumors in both human and animal hosts. Using an unbiased deep sequencing approach, we identified a novel, highly divergent polyomavirus, provisionally named MX polyomavirus (MXPyV), in stool samples from children. The ∼5.0 kB viral genome exhibits little overall homology (<46% amino acid identity) to known polyomaviruses, and, due to phylogenetic variation among its individual proteins, cannot be placed in any existing taxonomic group. PCR-based screening detected MXPyV in 28 of 834 (3.4%) fecal samples collected from California, Mexico, and Chile, and 1 of 136 (0.74%) of respiratory samples from Mexico, but not in blood or urine samples from immunocompromised patients. By quantitative PCR, the measured titers of MXPyV in human stool at 10% (weight/volume) were as high as 15,075 copies. No association was found between the presence of MXPyV and diarrhea, although girls were more likely to shed MXPyV in the stool than boys (p = 0.012). In one child, viral shedding was observed in two stools obtained 91 days apart, raising the possibility of chronic infection by MXPyV. A multiple sequence alignment revealed that MXPyV is a closely related variant of the recently reported MWPyV and HPyV10 polyomaviruses. Further studies will be important to determine the association, if any, of MXPyV with disease in humans.

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Available from: Eric Delwart, Jul 30, 2015
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    • "Reference databases of host and pathogen sequences range in size from 2 Gb for viruses to 3.1 Gb for the human genome to 42 Gb for all nucleotide sequences in the National Center for Biotechnology Information (NCBI) nucleotide (nt) collection (NCBI nt DB) as of January 2013. Second, only a small fraction of short NGS reads in clinical metagenomic data typically correspond to pathogens (a ''needle-in-a-haystack'' problem) (Kostic et al. 2012; Wylie et al. 2012; Yu et al. 2012), and such sparse reads often do not overlap sufficiently to permit de novo assembly into longer contiguous sequences (contigs) (Kostic et al. 2011). Thus, individual reads, typically only 100–300 nucleotides (nt) in length, must be classified to a high degree of accuracy. "
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    ABSTRACT: Unbiased next-generation sequencing (NGS) approaches enable comprehensive pathogen detection in the clinical microbiology laboratory and have numerous applications for public health surveillance, outbreak investigation, and the diagnosis of infectious diseases. However, practical deployment of the technology is hindered by the bioinformatics challenge of analyzing results accurately and in a clinically relevant timeframe. Here we describe SURPI ("sequence-based ultrarapid pathogen identification"), a computational pipeline for pathogen identification from complex metagenomic NGS data generated from clinical samples, and demonstrate use of the pipeline in the analysis of 237 clinical samples comprising more than 1.1 billion sequences. Deployable on both cloud-based and standalone servers, SURPI leverages two state-of-the-art aligners for accelerated analyses, SNAP and RAPSearch, which are as accurate as existing bioinformatics tools but orders of magnitude faster in performance. In fast mode, SURPI detects viruses and bacteria by scanning data sets of 7-500 million reads in 11 min to 5 h, while in comprehensive mode, all known microorganisms are identified, followed by de novo assembly and protein homology searches for divergent viruses in 50 min to 16 h. SURPI has also directly contributed to real-time microbial diagnosis in acutely ill patients, underscoring its potential key role in the development of unbiased NGS-based clinical assays in infectious diseases that demand rapid turnaround times.
    Genome Research 06/2014; 24(7). DOI:10.1101/gr.171934.113 · 13.85 Impact Factor
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    • "The human polyomavirus (HPyV) family today tentatively comprises 12 members [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13], the infections by which are widespread and initially apparently asymptomatic [14]. The eighth HPyV discovered is the TS polyomavirus (TSPyV), infecting approximately 70% of the world's population [15] [16] [17]. "
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    ABSTRACT: The trichodysplasia spinulosa-associated polyomavirus (TSPyV), a recently discovered species of the family Polyomaviridae, is associated with development of trichodysplasia spinulosa (TS), a rare follicular skin disease of immunocompromised individuals. The viral seroprevalence in the general population is ∼70%, with little known of its route of transmission, latency, or primary infection site. We aimed to determine whether the viral DNA is detectable in tonsillar tissue of constitutionally healthy individuals, and what the corresponding antiviral seroreactivities are. We tested 229 matched pairs of tonsillar tissue biopsies and serum samples from asymptomatic donors for TSPyV DNA by real-time quantitative PCR with primer pairs and Taq-Man probes targeting the VP1 and LT genes. The sera were studied by enzyme immunoassay (EIA) for TSPyV-VP1-IgG and the PCR-positive individuals also for -IgM and -IgG-avidity. TSPyV DNA was detectable in 8 (3.5%) of 229 tonsillar tissues, and in none of the corresponding sera. TSPyV IgG seroprevalence among children was 39% and among adults 70%. Each of the 8 PCR-positive subjects had antiviral IgG of high avidity but not IgM. TSPyV PCR positivity of tonsillar samples of individuals with long-term immunity provides the first evidence of TSPyV in tonsils and suggests lymphoid tissue as a latency site of this emerging human pathogen.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 11/2013; 59(1). DOI:10.1016/j.jcv.2013.11.008 · 3.47 Impact Factor
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    • "Whether HPyV10 was responsible for the warts or associated to any other disease or cancer was not been addressed, but most probably unlikely, since the sample also contained the papilloma causing human papillomavirus (HPV) type 6. Finally, very recently, in stools of children an HPyV designated MXPyV was described (Yu et al., 2012). This virus is a closely related variant of MWPyV and HPyV10, and the study thus confirmed that this tenth HPyV can frequently be found in stools. "
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    ABSTRACT: Today the human polyomavirus (HPyV) family consists of 10 members, BK virus (BKV) and JC virus (JCV) isolated 40 years ago and the more recently identified KI virus (KIPyV), WU virus (WUPyV), Merkel cell polyomavirus (MCPyV), HPyV6, HPyV7, trichodysplasia spinulosa virus (TSPyV), HPyV9 and MWPyV. Serological studies suggest that HPyVs subclinically infect the general population with rates ranging from 35% to 90%. However, significant disease is only observed in patients with impaired immune functions. Thus, BKV has been linked to hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation and PyV-associated nephropathy (PyVAN) after kidney transplantation; JCV to progressive multifocal leukoencephalopathy (PML) in HIV-AIDS, hematological diseases and in autoimmune diseases treated with certain lymphocyte-specific antibodies. KIPyV and WUPyV have been found in the respiratory tract, HPyV6 and 7 in the skin, and HPyV9 in serum and skin, and MWPyV in stools and skin, but so far none of these PyVs have been linked to any disease. TSPyV, on the other hand, was identified in trichodysplasia spinulosa, a rare skin disease characterized by virus-induced lytic as well as proliferative tumor-like features that is observed in immune-suppressed transplant patients. In contrast to all the other HPyVs so far, MCPyV is unique in its association with a cancer, Merkel cell carcinoma, which is a rare skin cancer arising in the elderly and chronically immunosuppressed individuals. The discovery of the new HPyVs has revived interest in the Polyomaviridae and their association to human disease and cancer. In this review, we summarize knowledge about this expanding family of human pathogens.
    Virology 01/2013; 437(2). DOI:10.1016/j.virol.2012.12.015 · 3.28 Impact Factor
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