Malawi Polyomavirus Is a Prevalent Human Virus That Interacts with Known Tumor Suppressors

Abstract

h Malawi polyomavirus (MWPyV) is a recently identified human polyomavirus. Serology for MWPyV VP1 indicates that infection frequently occurs in childhood and reaches a prevalence of 75% in adults. The MWPyV small T antigen (ST) binds protein phosphatase 2A (PP2A), and the large T antigen (LT) binds pRb, p107, p130, and p53. However, the MWPyV LT was less stable than the simian virus 40 (SV40) LT and was unable to promote the growth of normal cells. This report confirms that MWPyV is a widespread human virus expressing T antigens with low transforming potential. Polyomaviruses are small, nonenveloped, circular doublestranded DNA viruses that maintain persistent lifelong infections in humans and animals (1). Human polyomaviruses (HPyV), including JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV), can cause significant disease, primarily in immunocompromised individuals, with increased virus levels contributing to the progression of a disease state (1, 2). Since 2007, the identification of 11 new HPyV has brought renewed attention to this family of DNA tumor viruses and their potential role in human disease. For example, trichodysplasia spinulosa-associated polyomavirus (TSPyV) was isolated from severely immunocompromised patients with trichodysplasia spinulosa (3). The Merkel cell polyomavirus (MCPyV) was found to be clonally integrated into a large percentage of Merkel cell carcinomas (MCC), a cancer with risk factors that include advanced age, prolonged UV exposure, and immunosuppression due to HIV-1/AIDS, hematologic malignancy, or solid-organ transplantation (4, 5). However, many new HPyV have not yet been associated with disease. For example, although WU polyomavirus (WUPyV) (6) and KI polyomavirus (KIPyV) (7) were isolated from nasopharyngeal secretions of children, they do not appear to contribute to pneumonia or other pulmonary disorders. HPyV6 (8) and HPyV7 (8) were found to be chronically shed from the skin; HPyV7 was recently associated with a pruritic rash in certain immunocompromised individuals (9). HPyV9 (10) was found in blood and urine and has sequence similarity to the B-lymphotropic polyomavirus previously isolated from African green monkey cells (11).Malawi polyomavirus (MWPyV) (12), Saint Louis polyomavirus (STLPyV) (13), HPyV12 (14), and New Jersey polyomavirus (NJPyV) (15) are the most recently described HPyV. HPyV12 was isolated from resected human liver tissue, while NJPyV was found in endothelial cells of a pancreatic transplant patient. HPyV10 (16) and Mexico polyomavirus (MXPyV) (17) represent different isolates of MWPyV, while STLPyV, HPyV12, and NJPyV are genetically distinct HPyV species. MWPyV/MXPyV and STLPyV were isolated from human stool samples in children presenting with diarrhea. MWPyV and HPyV10 were also isolated from a wart in a patient with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome. WHIM syndrome increases patient susceptibility to human papillomavirus (HPV) infection (18). It is possible that MWPyV/HPyV10 contributed to the development ...

Seroprevalence rates of HPyV6, HPyV7, TSPyV, HPyV9, MWPyV and KIPyV polyomaviruses among the healthy blood donors

“…Seroprevalence to MWPyV (84.4%) was the second highest from all of HPyVs tested. Two recent studies reported MWPyV 42–75% in adulthood [Nicol et al, ; Berrios et al, ], which is slightly lower number compared to our findings. Seroprevalence to KIPyV (58%) agrees with numbers (55–70%) reported by others [Nguyen et al, ; Neske et al, ; Nicol et al, , ].…”

Merkel Cell Polyomavirus Small T Antigen Promotes Pro-Glycolytic Metabolic Perturbations Required for Transformation

“…IMR90 proliferation assays were performed as previously described [60]. Briefly, IMR90 cell lines were seeded in triplicate in 24-well plates (day 0; 5 x 10 3 cells per well).…”

Quantitative detection of human Malawi polyomavirus in nasopharyngeal aspirates, sera, and feces in Beijing, China, using real-time TaqMan-based PCR

“…Several studies have reported the widespread distribution of MWPyV in different areas of the world, including Africa, the USA, Asia, Italy, Australia, and South America [5,[11][12][13][14][15]. In this study, we used a qPCR assay to rapidly and accurately screen for MWPyV in NPA, serum, and fecal samples collected from different populations in China.…”