Exploring the Lifecycle, Pathophysiology, and Potential Therapeutic Applications of the Reovirus: Exploring Therapeutic Applications of the Reovirus

Anwaar  Iftikhar; Rida Farooq; Muhammad  Ali; Zaroon Gill; Usama  Mustafa; Haleema  Khalid; Mubeen  Akhtar; Ruhma  Maqsood; Sana  Hussain; Maryam  Munir

doi:10.54393/pbmj.v6i09.932

Authors

Anwaar Iftikhar Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
Rida Farooq Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
Muhammad Ali Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
Zaroon Gill Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
Usama Mustafa Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
Haleema Khalid Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
Mubeen Akhtar Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
Ruhma Maqsood Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
Sana Hussain Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
Maryam Munir Department of Zoology, University of the Punjab, Lahore, Pakistan

DOI:

https://doi.org/10.54393/pbmj.v6i09.932

Keywords:

Reovirus,, Viral Therapeutics, Oncolytic viruses, Diseases, Viruses Human Papillomavirus

Abstract

The Reoviridae family of double-stranded RNA viruses includes Reovirus. Both humans and animals might become sick from it. Even though they are often benign, certain strains have been connected to significant illnesses. This review investigates the virus's structure, replication, pathogenesis, clinical significance, and potential therapies. Its unusual capsid form is made up of a segmented genome that encodes twelve proteins and two concentric protein shells. Replication involves uncoating, receptor binding, endocytosis, genome transcription, and cytoplasmic translation. Reovirus masterfully manipulates its host's cellular functions, inducing apoptosis and stress responses that help it spread and multiply. Recently, encephalitis, myocarditis, and maybe even certain cancers have been linked to reovirus, which often produces mild respiratory or gastrointestinal symptoms. To fully understand the viral-host interactions producing these illnesses, further research is necessary. Particularly, the reovirus has promise for oncolytic virotherapy. Whether used alone or in conjunction with other medicines, a range of cancer types have showed positive outcomes in clinical studies. In essence, reovirus is a versatile pathogen that has intimate relationships with its hosts. To realize its therapeutic potential and shed light on its pathogenesis, one must have a complete grasp of its molecular and cellular connections. Unlocking the virus's potential is necessary to predict how it will impact both human and animal health.

References

Alemany R, Balagué C, Curiel DT. Replicative adenoviruses for cancer therapy. Nature Biotechnology. 2000 Jul; 18(7): 723-7. doi: 10.1038/77283. DOI: https://doi.org/10.1038/77283

Arnaboldi S, Righi F, Filipello V, Trogu T, Lelli D, Bianchi A, et al. Mammalian orthoreovirus (MRV) is widespread in wild ungulates of Northern Italy. Viruses. 2021 Feb; 13(2): 238. doi: 10.3390/v13020238. DOI: https://doi.org/10.3390/v13020238

Barton ES, Forrest JC, Connolly JL, Chappell JD, Liu Y, Schnell FJ, et al. Junction adhesion molecule is a receptor for reovirus. Cell. 2001 Feb; 104(3): 441-51. doi: 10.1016/S0092-8674(01)00231-8. DOI: https://doi.org/10.1016/S0092-8674(01)00231-8

Benavente J and Martínez-Costas J. Avian reovirus: structure and biology. Virus research. 2007 Feb; 123(2): 105-19. doi: 10.1016/j.virusres.2006.09.005. DOI: https://doi.org/10.1016/j.virusres.2006.09.005

Berkeley RA, Steele LP, Mulder AA, Van Den Wollenberg DJ, Kottke TJ, Thompson J, et al. Antibody-neutralized reovirus is effective in oncolytic virotherapy. Cancer immunology research. 2018 Oct; 6(10): 1161-73. doi: 10.1158/2326-6066.CIR-18-0309. DOI: https://doi.org/10.1158/2326-6066.CIR-18-0309

Berton-Rigaud D, Vergote I, Pautier P, Kryzhanivska A, Angelergues A, Kornacki D, et al. A phase 1 study of retifanlimab (INCMGA00012), a PD-1 inhibitor, in patients with advanced solid tumors: Preliminary results in recurrent MSI-high or dMMR endometrial cancer (POD1UM-101). Journal of Immunotherapy Cancer. 2020 Dec; 8(3): A164–5; doi: 10.1136/jitc-2020-SITC2020.0268. DOI: https://doi.org/10.1136/jitc-2020-SITC2020.0268

Bouziat R, Hinterleitner R, Brown JJ, Stencel-Baerenwald JE, Ikizler M, Mayassi T, et al. Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science. 2017 Apr; 356(6333): 44-50. doi: 10.1126/science. aah5298. DOI: https://doi.org/10.1126/science.aah5298

Carroll K, Hastings C, Miller CL. Amino acids 78 and 79 of mammalian orthoreovirus protein µNS are necessary for stress granule localization, core protein λ2 interaction, and de novo virus replication. Virology. 2014 Jan; 448: 133-45. doi: 10.1016/j.virol.2013.10.009 DOI: https://doi.org/10.1016/j.virol.2013.10.009

Chandran K, Zhang X, Olson NH, Walker SB, Chappell JD, Dermody TS, et al. Complete in vitro assembly of the reovirus outer capsid produces highly infectious particles suitable for genetic studies of the receptor-binding protein. Journal of Virology. 2001 Jun; 75(11): 5335-42. doi: 10.1128/JVI.75.11.5335-5342.2001. DOI: https://doi.org/10.1128/JVI.75.11.5335-5342.2001

Chou J, Lin YC, Kim J, You L, Xu Z, He B, et al. Nasopharyngeal carcinoma—review of the molecular mechanisms of tumorigenesis. Head & Neck: Journal for the Sciences and Specialties of the Head and Neck. 2008 Jul; 30(7): 946-63. doi: 10.1002/hed.20833. DOI: https://doi.org/10.1002/hed.20833

Chua KB, Voon K, Crameri G, Tan HS, Rosli J, McEachern JA, et al. Identification and characterization of a new orthoreovirus from patients with acute respiratory infections. PloS One. 2008 Nov; 3(11): e3803. doi: 10.1371/journal.pone.0003803. DOI: https://doi.org/10.1371/journal.pone.0003803

Clarke P and Tyler KL. Reoviruses: General Features. In: Encyclopedia of Virology (Third Edition). (Mahy BWJVan Regenmortel MHV. eds.) Academic Press: Cambridge, MA; 2008; 382–90. doi: 10.1016/b978-012374410-4.00484-2. DOI: https://doi.org/10.1016/B978-012374410-4.00484-2

Zuckerman AJ. Fields virology, 3rd edition. (two vol. set). FEBS Letters. 1996 Jun; 388(1): 88–88. doi: 10.1016/0014-5793(96)88179-8. DOI: https://doi.org/10.1016/0014-5793(96)88179-8

Demidenko AA, Blattman JN, Blattman NN, Greenberg PD, Nibert ML. Engineering recombinant reoviruses with tandem repeats and a tetravirus 2A-like element for exogenous polypeptide expression. Proceedings of the National Academy of Sciences. 2013 May; 110(20): E1867-76. doi: 10.1073/pnas.1220107110 DOI: https://doi.org/10.1073/pnas.1220107110

Dock G. The influence of complicating diseases upon leukaemia. The American Journal of the Medical Sciences (1827-1924). 1904 Apr; 127(4): 563. DOI: https://doi.org/10.1097/00000441-190412740-00001

Duncan R. Extensive sequence divergence and phylogenetic relationships between the fusogenic and nonfusogenic orthoreoviruses: a species proposal. Virology. 1999 Aug; 260(2): 316-28. doi: 10.1006/viro.1999.9832. DOI: https://doi.org/10.1006/viro.1999.9832

Ebert DH, Deussing J, Peters C, Dermody TS. Cathepsin L and cathepsin B mediate reovirus disassembly in murine fibroblast cells. Journal of Biological Chemistry. 2002 Jul; 277(27): 24609-17. doi: 10.1074/jbc.M201107200. DOI: https://doi.org/10.1074/jbc.M201107200

Eigl BJ, Chi K, Tu D, Hotte SJ, Winquist E, Booth CM, et al. A randomized phase II study of pelareorep and docetaxel or docetaxel alone in men with metastatic castration resistant prostate cancer: CCTG study IND 209. Oncotarget. 2018 Jan; 9(8): 8155. doi: 10.18632/oncotarget.24263. DOI: https://doi.org/10.18632/oncotarget.24263

Fernández de Castro I, Tenorio R, Ortega-González P, Knowlton JJ, Zamora PF, Lee CH, et al. A modified lysosomal organelle mediates nonlytic egress of reovirus. Journal of Cell Biology. 2020 May; 219(7): e201910131. doi: 10.1083/jcb.201910131. DOI: https://doi.org/10.1083/jcb.201910131

Fernández de Castro I, Zamora PF, Ooms L, Fernández JJ, Lai CM, Mainou BA, et al. Reovirus forms neo-organelles for progeny particle assembly within reorganized cell membranes. MBio. 2014 Feb; 5(1): 10-128. DOI: https://doi.org/10.1128/mBio.00931-13

Garant KA, Shmulevitz M, Pan L, Daigle RM, Ahn DG, Gujar SA, et al. Oncolytic reovirus induces intracellular redistribution of Ras to promote apoptosis and progeny virus release. Oncogene. 2016 Feb; 35(6): 771-82. doi: 10.1038/onc.2015.136. DOI: https://doi.org/10.1038/onc.2015.136

Goel S, Ocean AJ, Parakrama RY, Ghalib MH, Chaudhary I, Shah U, et al. Elucidation of pelareorep pharmacodynamics in a phase I trial in patients with KRAS-mutated colorectal cancer. Molecular Cancer Therapeutics. 2020 May;19(5): 1148-56. doi: 10.1158/1535-7163.MCT-19-1117. DOI: https://doi.org/10.1158/1535-7163.MCT-19-1117

Hingorani P, Zhang W, Lin J, Liu L, Guha C, Kolb EA. Systemic administration of reovirus (Reolysin) inhibits growth of human sarcoma xenografts. Cancer. 2011 Apr; 117(8): 1764-74. doi: 10.1002/cncr.25741. DOI: https://doi.org/10.1002/cncr.25741

Ikeda Y, Nishimura G, Yanoma S, Kubota A, Furukawa M, Tsukuda M. Reovirus oncolysis in human head and neck squamous carcinoma cells. Auris Nasus Larynx. 2004 Dec; 31(4): 407-12. doi: 10.1016/j.anl.2004.07.003. DOI: https://doi.org/10.1016/S0385-8146(04)00111-7

Jacobs BL and Samuel CE. Biosynthesis of reovirus-specified polypeptides: the reovirus s1 mRNA encodes two primary translation products. Virology. 1985 May; 143(1): 63-74. doi: 10.1016/0042-6822(85)90097-2. DOI: https://doi.org/10.1016/0042-6822(85)90097-2

Kanai Y, Kawagishi T, Matsuura Y, Kobayashi T. In vivo live imaging of oncolytic mammalian orthoreovirus expressing NanoLuc luciferase in tumor xenograft mice. Journal of Virology. 2019 Jul; 93(14): 10-128. doi: 10.1128/JVI.00401-19. DOI: https://doi.org/10.1128/JVI.00401-19

Knowlton JJ, Fernandez de Castro I, Ashbrook AW, Gestaut DR, Zamora PF, Bauer JA, et al. The TRiC chaperonin controls reovirus replication through outer-capsid folding. Nature Microbiology. 2018 Apr; 3(4): 481-93. doi: 10.1038/s41564-018-0122-x. DOI: https://doi.org/10.1038/s41564-018-0122-x

Lai CM, Mainou BA, Kim KS, Dermody TS. Directional release of reovirus from the apical surface of polarized endothelial cells. MBio. 2013 May; 4(2): 10-128. doi: 10.1128/mBio.00049-13. DOI: https://doi.org/10.1128/mBio.00049-13

Lim MC, Wang YF, Huang SW, Yang JY, Wang JR. High incidence of mammalian orthoreovirus identified by environmental surveillance in Taiwan. PLoS One. 2015 Nov; 10(11): e0142745. doi: 10.1371/journal.pone.0142745. DOI: https://doi.org/10.1371/journal.pone.0142745

Maitra R, Seetharam R, Tesfa L, Augustine TA, Klampfer L, Coffey MC, et al. Oncolytic reovirus preferentially induces apoptosis in KRAS mutant colorectal cancer cells, and synergizes with irinotecan. Oncotarget. 2014 May; 5(9): 2807. doi: 10.18632/oncotarget.1921. DOI: https://doi.org/10.18632/oncotarget.1921

Miller CL, Broering TJ, Parker JS, Arnold MM, Nibert ML. Reovirus σNS protein localizes to inclusions through an association requiring the μNS amino terminus. Journal of Virology. 2003 Apr; 77(8): 4566-76. doi: 10.1128/jvi.77.8.4566-4576.2003. DOI: https://doi.org/10.1128/JVI.77.8.4566-4576.2003

Morris DG, Feng X, DiFrancesco LM, Fonseca K, Forsyth PA, Paterson AH, et al. REO-001: A phase I trial of percutaneous intralesional administration of reovirus type 3 dearing (Reolysin®) in patients with advanced solid tumors. Investigational New Drugs. 2013 Jun; 31: 696-706. doi: 10.1007/s10637-012-9865-z. DOI: https://doi.org/10.1007/s10637-012-9865-z

Niu X, Zhang B, Yu X, Zhang X, Dou Y, Tang Y, et al. Preparation and evaluation of goose reovirus inactivated vaccine. BMC Veterinary Research. 2017 Dec; 13: 1-9. doi: 10.1186/s12917-017-1134-0. DOI: https://doi.org/10.1186/s12917-017-1134-0

Olson NO. Transmissible synovitis of poultry. Laboratory investigation; a journal of Technical Methods and Pathology. 1959 Nov; 8: 1384-93.

Roner MR, Sutphin LA, Joklik WK. Reovirus RNA is infectious. Virology. 1990 Dec; 179(2): 845-52. doi: 10.1016/0042-6822(90)90153-i. DOI: https://doi.org/10.1016/0042-6822(90)90153-I

Tai JH, Williams JV, Edwards KM, Wright PF, Crowe Jr JE, Dermody TS. Prevalence of reovirus-specific antibodies in young children in Nashville, Tennessee. The Journal of Infectious Diseases. 2005 Apr; 191(8): 1221-4. doi: 10.1086/428911. DOI: https://doi.org/10.1086/428911

Twigger K, Vidal L, White CL, De Bono JS, Bhide S, Coffey M, et al. Enhanced in vitro and in vivo cytotoxicity of combined reovirus and radiotherapy. Clinical Cancer Research. 2008 Feb; 14(3): 912-23. doi: 10.1158/1078-0432.CCR-07-1400. DOI: https://doi.org/10.1158/1078-0432.CCR-07-1400

Zou S, Brown EG. Translation of the reovirus M1 gene initiates from the first AUG codon in both infected and transfected cells. Virus Research. 1996 Jan; 40(1): 75-89. doi: 10.1016/0168-1702(95)01261-3. DOI: https://doi.org/10.1016/0168-1702(95)01261-3

Zamarin D and Palese P. Oncolytic Newcastle disease virus for cancer therapy: old challenges and new directions. Future Microbiology. 2012 Mar; 7(3): 347-67. doi: 10.2217/fmb.12.4. DOI: https://doi.org/10.2217/fmb.12.4

Makker J, Bajantri B, Sakam S, Chilimuri S. Cytomegalovirus related fatal duodenal diverticular bleeding: case report and literature review. World Journal of Gastroenterology. 2016 Aug; 22(31): 7166. doi: 10.3748/wjg.v22.i31.7166. DOI: https://doi.org/10.3748/wjg.v22.i31.7166