Murine norovirus explained

Murine norovirus (MNV) is a species of norovirus affecting mice. It was first identified in 2003.[1] MNV is commonly used in research to model Human norovirus[2] because the latter is difficult to grow in the laboratory. Standardized cell cultures are used in MNV propagation and the virus naturally infects mice, which allows studies in animal systems.[3]

Virology

Genetics

Like all noroviruses, MNV has linear, non-segmented,[4] positive-sense RNA genome of approximately 7.5 kbp, encoding a large polyprotein which is cleaved into six smaller non-structural proteins (NS1/2 to NS7)[5] by the viral 3C-like protease (NS6), a major structural protein (VP1) of about 58~60 kDa and a minor capsid protein (VP2).[6] In addition to these proteins, MNV is unique amongst the noroviruses in possessing an additional fourth open reading frame overlapping the VP1 coding sequence. This additional reading frame encodes a virulence factor (VF1) which regulates the innate immune response.[7] The 3'UTR of the viral genome forms stem-loop structures which have a role in virulence.[8]

Entry

Entry mechanisms for noroviruses are still largely unknown,[9] but the first proteinaceous receptor mediating norovirus entry was found with experiments on MNV. This receptor, CD300lf, is a membrane glycoprotein, that functions in regulation of multiple immune responses.[10] CD300lf is found on mast cells of both murine species and humans, but definite proof of its function in human norovirus infections remains unknown. In mice however, CD300lf functions in virus binding[11] thus having a role to play in the first steps of viral entry. Binding is essentially mediated by phospholipids of the virus' VP1 protein that bind to a cleft between CDR3 and CC’loop -domains of CD300lf -receptor.[12] [13]

Notes and References

  1. Karst SM, Wobus CE, Lay M, Davidson J, Virgin HW . STAT1-dependent innate immunity to a Norwalk-like virus . Science . 299 . 5612 . 1575–8 . March 2003 . 12624267 . 10.1126/science.1077905 . 2003Sci...299.1575K . 10044606 .
  2. Oka T, Stoltzfus GT, Zhu C, Jung K, Wang Q, Saif LJ . Attempts to grow human noroviruses, a sapovirus, and a bovine norovirus in vitro . PLOS ONE . 13 . 2 . e0178157 . 2018-02-13 . 29438433 . 5810978 . 10.1371/journal.pone.0178157 . 2018PLoSO..1378157O . free .
  3. Vashist S, Bailey D, Putics A, Goodfellow I . Model systems for the study of human norovirus Biology . Future Virology . 4 . 4 . 353–367 . July 2009 . 21516251 . 3079900 . 10.2217/fvl.09.18 .
  4. Web site: Viral Zone. ExPASy. 15 June 2015.
  5. Thorne LG, Goodfellow IG . Norovirus gene expression and replication . The Journal of General Virology . 95 . Pt 2 . 278–91 . February 2014 . 24243731 . 10.1099/vir.0.059634-0 . free .
  6. Clarke IN, Lambden PR . Organization and expression of calicivirus genes . The Journal of Infectious Diseases . 181 . S309-16 . May 2000 . Suppl 2 . 10804143 . 10.1086/315575 . free .
  7. McFadden N, Bailey D, Carrara G, Benson A, Chaudhry Y, Shortland A, Heeney J, Yarovinsky F, Simmonds P, Macdonald A, Goodfellow I . Norovirus regulation of the innate immune response and apoptosis occurs via the product of the alternative open reading frame 4 . PLOS Pathogens . 7 . 12 . e1002413 . December 2011 . 22174679 . 3234229 . 10.1371/journal.ppat.1002413 . free .
  8. Bailey D, Karakasiliotis I, Vashist S, Chung LM, Rees J, Reese J, McFadden N, Benson A, Yarovinsky F, Simmonds P, Goodfellow I . 6 . Functional analysis of RNA structures present at the 3' extremity of the murine norovirus genome: the variable polypyrimidine tract plays a role in viral virulence . Journal of Virology . 84 . 6 . 2859–70 . March 2010 . 20053745 . 2826041 . 10.1128/JVI.02053-09 .
  9. Bartnicki E, Cunha JB, Kolawole AO, Wobus CE . Recent advances in understanding noroviruses . F1000Research . 6 . 79 . 2017-01-26 . 28163914 . 5270584 . 10.12688/f1000research.10081.1 . free .
  10. Voss OH, Tian L, Murakami Y, Coligan JE, Krzewski K . Emerging role of CD300 receptors in regulating myeloid cell efferocytosis . Molecular & Cellular Oncology . 2 . 4 . e964625 . 2015-10-02 . 27308512 . 4905414 . 10.4161/23723548.2014.964625 .
  11. Orchard RC, Wilen CB, Doench JG, Baldridge MT, McCune BT, Lee YC, Lee S, Pruett-Miller SM, Nelson CA, Fremont DH, Virgin HW . Discovery of a proteinaceous cellular receptor for a norovirus . Science . 353 . 6302 . 933–6 . August 2016 . 27540007 . 5484048 . 10.1126/science.aaf1220 . 2016Sci...353..933O .
  12. Nelson CA, Wilen CB, Dai YN, Orchard RC, Kim AS, Stegeman RA, Hsieh LL, Smith TJ, Virgin HW, Fremont DH . Structural basis for murine norovirus engagement of bile acids and the CD300lf receptor . Proceedings of the National Academy of Sciences of the United States of America . 115 . 39 . E9201–E9210 . September 2018 . 30194229 . 6166816 . 10.1073/pnas.1805797115 . 2018PNAS..115E9201N . free .
  13. Haga K, Fujimoto A, Takai-Todaka R, Miki M, Doan YH, Murakami K, Yokoyama M, Murata K, Nakanishi A, Katayama K . Functional receptor molecules CD300lf and CD300ld within the CD300 family enable murine noroviruses to infect cells . Proceedings of the National Academy of Sciences of the United States of America . 113 . 41 . E6248–E6255 . October 2016 . 27681626 . 5068309 . 10.1073/pnas.1605575113 . 2016PNAS..113E6248H . free .

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