Murine and related chapparvoviruses are nephro-tropic and produce novel accessory proteins in infected kidneys

Autor(es):Mostrar menos -

Lee, Quintin ^[1] ; Padula, Matthew P. ^[2] ; Pinello, Natalia ^[1] ; Williams, Simon H. ^[3] ; O'Rourke, Matthew B. ^[4] ; Fumagalli, Marcilio Jorge ^[5] ; Orkin, Joseph D. ^{[6, 7]} ; Song, Renhua ^[1] ; Shaban, Babak ^[8] ; Brenner, Ori ^[9] ; Pimanda, John E. ^[10] ; Weninger, Wolfgang ^{[1, 11]} ; de Souza, William Marciel ^[5] ; Melin, Amanda D. ^{[7, 12, 13]} ; Wong, Justin J-L ^[1] ; Crim, Marcus J. ^[14] ; Monette, Sebastien ^[15] ; Roediger, Ben ^{[1, 16]} ; Jolly, Christopher J. ^[10]

Afiliação do(s) autor(es):Mostrar menos -

^[1] Univ Sydney, Centenary Inst, Fac Med & Hlth, Sydney, NSW - Australia

^[2] Univ Technol Sydney, Prote Core Facil, Sydney, NSW - Australia

^[3] Columbia Univ, Mailman Sch Publ Hlth, Ctr Infect & Immun, New York, NY - USA

^[4] Univ Sydney, Fac Med & Hlth, Kolling Inst Med Res, Sydney, NSW - Australia

^[5] Univ Sao Paulo, Sch Med Ribeirao Preto, Virol Res Ctr, Ribeirao Preto - Brazil

^[6] Univ Calgary, Dept Anthropol & Archaeol, Calgary, AB - Canada

^[7] Univ Pompeu Fabra, CSIC, Inst Biol Evolut, Barcelona - Spain

^[8] Univ Melbourne, Melbourne Integrat Genom, Melbourne, Vic - Australia

^[9] Weizmann Inst Sci, Dept Vet Resources, Rehovot - Israel

^[10] Univ New South Wales Sydney, Lowy Canc Res Ctr, Sydney, NSW - Australia

^[11] Med Univ Vienna, Dept Dermatol, Vienna - Austria

^[12] Univ Calgary, Dept Med Genet, Cumming Sch Med, Calgary, AB - Canada

^[13] Univ Calgary, Alberta Childrens Hosp, Res Inst, Cumming Sch Med, Calgary, AB - Canada

^[14] IDEXX BioAnalytics, Microbiol & Aquat Diagnost, Discovery Dr, Columbia, MO - USA

^[15] Rockefeller Univ, Weill Cornell Med New, Lab Comparat Pathol, Ctr Comparat Med & Pathol, Mem Sloan Kettering Can, 1230 York Ave, New York, NY 10021 - USA

^[16] Novartis Inst Biomed Res, Autoimmun Transplantat Inflammat ATI Dis Area, Basel - Switzerland

• Tipo de documento: Artigo Científico
• Fonte: PLOS PATHOGENS; v. 16, n. 1 JAN 2020.
• Citações Web of Science: 0

Resumo

Mouse kidney parvovirus (MKPV) is a member of the provisional genus Chapparvovirus that causes renal disease in immune-compromised mice, with a disease course reminiscent of polyomavirus-associated nephropathy in immune-suppressed kidney transplant patients. Here we map four major MKPV transcripts, created by alternative splicing, to a common initiator region, and use mass spectrometry to identify ``p10{''} and ``p15{''} as novel chapparvovirus accessory proteins produced in MKPV-infected kidneys. p15 and the splicing-dependent putative accessory protein NS2 are conserved in all near-complete amniote chapparvovirus genomes currently available (from mammals, birds and a reptile). In contrast, p10 may be encoded only by viruses with >60% amino acid identity to MKPV. We show that MKPV is kidney-tropic and that the bat chapparvovirus DrPV-1 and a non-human primate chapparvovirus, CKPV, are also found in the kidneys of their hosts. We propose, therefore, that many mammal chapparvoviruses are likely to be nephrotropic. Author summary Parvoviruses are small, genetically simple single-strand DNA viruses that remain viable outside their hosts for very long periods of time. They cause disease in several domesticated species and in humans. Mouse kidney parvovirus (MKPV) is a causative agent of kidney failure in immune-compromised mice and is the only member of the provisional Chapparvovirus genus for which the complete genome including telomeres is known. Here, we show that MKPV propagates almost exclusively in the kidneys of mice infected naturally, wherein it produces novel accessory proteins whose coding regions are conserved in amniote-associated chapparvovirus sequences. We assemble a closely related complete viral genome present in DNA extracted from the kidney of a wild Cebus imitator monkey, and show that another related chapparvovirus is preferentially found in kidneys of the vampire bat Desmodus rotundus. We conclude that many mammal-hosted chapparvovirus are adapted to the kidney niche and may therefore cause disease following kidney stress in multiple species. (AU)

• Processo FAPESP: 17/13981-0 - Caracterização, genômica e diagnóstico de vírus com importância em saúde pública no Brasil por sequenciamento de alto desempenho
• Beneficiário: William Marciel de Souza
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/09383-3 - Estudo sobre epitopos de Flavivirus com importância médica no Brasil e de seus anticorpos
• Beneficiário: Marcilio Jorge Fumagalli
• Modalidade de apoio: Bolsas no Brasil - Doutorado