Minute virus of mice

Minute virus of mice (MVM) is the exemplar virus of the type 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]

Minute virus of mice
Virus classification
(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

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]

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References
  1. "ICTV 10th Report (2018)Protoparvovirus".
  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. 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. ISBN 978-0-340-81198-6.
  7. 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. 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. 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. 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.
  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.
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