Minute virus of mice

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Minute virus of mice
Minute virus of mice (MVM) (8811688398).jpg
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Monodnaviria
Kingdom: Shotokuvirae
Phylum: Cossaviricota
Class: Quintoviricetes
Order: Piccovirales
Family: Parvoviridae
Genus: Protoparvovirus
Species:
Rodent protoparvovirus 1
Virus:
Minute virus of mice

Minute virus of mice (MVM) is the exemplar virus of the species Rodent protoparvovirus 1 , in the genus Protoparvovirus [1] of the Parvoviridae family of viruses. [2] MVM exists in multiple variant forms including MVMp, which is the prototype strain that infects cells of fibroblast origin, while MVMi, the immunosuppressive strain, infects T lymphocytes. [3] MVM is a common infection in laboratory mice due to its highly contagious nature. [4] The virus can be shed from infected mice via feces and urine, but also via fomites and nasal secretions. [4] Typically there are no clinical signs of infection in adult mice, however, experimental infection can cause multiple organ damage during fetal development or shortly after birth. [4]

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Transcription profile

MVM uses two transcriptional promoters at map units (mu) 4 and 38 (p4 and p38) and a single polyadenylation site at mu 95 to create 3 major size classes of mRNAs, referred to as R1, R2 and R3, all of which have a short intron sequence between 46–48 mu removed. [5] R1 is produced from p4 and is translated into non-structural protein 1 (NS1). However, in some P4 transcripts a second intron between 10–40 mu is also excised, creating R2 mRNAs that encode NS2 proteins of ~25 kDa. These share 85 amino acids of N-terminal sequence with NS1, and then splice into an alternate reading frame before finally reaching the short central intron where 2 different C-terminal hexapeptides can be added. The R3 transcript produces capsid proteins VP1 and VP2, which requires transcription from the P38 promoter, in contrast to the P4 promoter used for transcripts R1 and R2. [1] [6]

Non-structural protein functions

NS1 functions as a required replication protein and is known to have helicase activity, [7] ATPase activity [7] and nickase activity. [8] Specifically, the nickase activity is required to resolve replication intermediate telomeres on the right-hand of the genome. [8] NS2 is known to exist in several spliced forms (isoforms) termed NS2-P, -Y and –L due to differences in the C-terminus of the isoforms as a result of alternative splicing. [9] NS2 is known to exist is both the cytoplasm and nucleus as well as in phosphorylated and non-phosphorylated forms. [9] In addition, NS2 is required for efficient infection in its natural murine host, but is dispensable in experimental infection in human cell lines. [9] Although not fully understood, in murine A9 fibroblasts NS2 interacts with nuclear export factor Crm1 resulting in efficient nuclear egress of progeny virions. [9]

DNA damage response

MVM induces a DNA damage response (DDR) during infection which is required for effective replication. [10] The ATM pathway is exclusively activated with a primarily Chk2-mediated response. [10] It is not known if viral proteins or active viral replication activate the DDR, but UV-inactivated MVM does not induce a response [10] suggesting that presence of MVM virions or MVM genome alone cannot cause the observed DDR activation.

Commercial uses

The Minute virus of Mice is currently the smallest virus that can be easily titrated to high levels; as such it is commercially used as a "worst case" example of a very small virus. [11] [12]

Related Research Articles

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<span class="mw-page-title-main">Hepatitis C virus</span> Species of virus

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<span class="mw-page-title-main">Adeno-associated virus</span> Species of virus

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<i>Pestivirus</i> Genus of viruses

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<i>Protoparvovirus</i> Genus of viruses

Protoparvovirus is a genus of viruses in the Parvovirinae subfamily of the virus family Parvoviridae. Vertebrates serve as natural hosts. There are 15 species in the genus including Rodent protoparvovirus 1 for which the exemplar virus is minute virus of mice (MVM). This genus also includes canine parvovirus (CPV), which causes gastrointestinal tract damage in puppies that is about 80% fatal, and porcine parvovirus (PPV), which is a major cause of fetal death and infertility in pigs. The genus divides phylogenetically into two branches, one that contains many founder members of the family, such as MVM, CPV and PPV, which have been studied in considerable detail, and a second branch occupied exclusively by predicted viruses whose coding sequences were identified recently in the wild using virus discovery approaches, but whose biology remains minimally explored. This second branch currently contains two species whose members infect humans, called Primate protoparvovirus 1 and Primate protoparvovirus 3. Until 2014, the genus was called Parvovirus, but it was renamed to eliminate confusion between members of this genus and members of the entire family Parvoviridae.

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References

  1. 1 2 "ICTV 10th Report (2018)Protoparvovirus".[ dead link ]
  2. ↑ "ICTV 10th Report (2018)Parvoviridae".
  3. ↑ Brownstein, David G.; Smith, Abigail L.; Johnson, Elizabeth A.; Pintel, David J.; Naeger, Lisa Kay; Tattersall, Peter (1992). "The pathogenesis of infection with minute virus of mice depends on expression of the small nonstructural protein NS2 and on the genotype of the allotropic determinants VP1 and VP2". Journal of Virology. 66 (5): 3118–24. doi:10.1128/JVI.66.5.3118-3124.1992. PMC   241074 . PMID   1373202.
  4. 1 2 3 Baker, David G. (1998). "Natural pathogens of laboratory mice, rats, and rabbits and their effects on research". Clinical Microbiology Reviews. 11 (2): 231–66. doi:10.1128/CMR.11.2.231. PMC   106832 . PMID   9564563.
  5. ↑ Naeger, L K; Schoborg, R V; Zhao, Q; Tullis, G E; Pintel, D J (1992). "Nonsense mutations inhibit splicing of MVM RNA in cis when they interrupt the reading frame of either exon of the final spliced product". Genes & Development. 6 (6): 1107–19. doi: 10.1101/gad.6.6.1107 . PMID   1592259.
  6. ↑ Kerr, Jonathan; Cotmore, Susan; Bloom, Marshall E, eds. (2005). Parvoviruses. CRC. pp. 253–256. ISBN   978-0-340-81198-6.
  7. 1 2 Nüesch, Jürg P. F.; Corbau, Romuald; Tattersall, Peter; Rommelaere, Jean (1998). "Biochemical activities of minute virus of mice nonstructural protein NS1 are modulated In vitro by the phosphorylation state of the polypeptide". Journal of Virology. 72 (10): 8002–12. doi:10.1128/JVI.72.10.8002-8012.1998. PMC   110136 . PMID   9733839.
  8. 1 2 Willwand, K; Deleu, L; Baldauf, A Q; Rommelaere, J; Beard, P; Costello, E; Mumtsidu, E (1997). "The minute virus of mice (MVM) nonstructural protein NS1 induces nicking of MVM DNA at a unique site of the right-end telomere in both hairpin and duplex conformations in vitro". Journal of General Virology. 78 (10): 2647–55. doi: 10.1099/0022-1317-78-10-2647 . PMID   9349487.
  9. 1 2 3 4 Eichwald, V.; Daeffler, L.; Klein, M.; Rommelaere, J.; Salome, N. (2002). "The NS2 Proteins of Parvovirus Minute Virus of Mice Are Required for Efficient Nuclear Egress of Progeny Virions in Mouse Cells". Journal of Virology. 76 (20): 10307–19. doi:10.1128/JVI.76.20.10307-10319.2002. PMC   136550 . PMID   12239307.
  10. 1 2 3 Adeyemi, Richard O.; Landry, Sebastien; Davis, Meredith E.; Weitzman, Matthew D.; Pintel, David J. (2010). "Parvovirus Minute Virus of Mice Induces a DNA Damage Response That Facilitates Viral Replication". PLOS Pathogens. 6 (10): e1001141. doi: 10.1371/journal.ppat.1001141 . PMC   2951379 . PMID   20949077.
  11. ↑ Weaver, Justin; Husson, Scott M.; Murphy, Louise; Wickramasinghe, S. Ranil (2013). "Anion exchange membrane adsorbers for flow-through polishing steps: Part I. clearance of minute virus of mice". Biotechnology and Bioengineering. 110 (2): 491–9. doi: 10.1002/bit.24720 . PMID   22949170. S2CID   38607484.
  12. ↑ Liu, S.; Carroll, M.; Iverson, R.; Valera, C.; Vennari, J.; Turco, K.; Piper, R.; Kiss, R.; Lutz, H. (2000). "Development and Qualification of a Novel Virus Removal Filter for Cell Culture Applications". Biotechnology Progress. 16 (3): 425–34. doi:10.1021/bp000027m. PMID   10835245. S2CID   25493791.
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