MOLECULAR INSIGHTS INTO THE MECHANISMS OF RABIES VIRUS NEUROINVASION AND PATHOGENICITY: A REVIEW ARTICLE

Abstract

Rabies is a major global health problem that kills approximately 59,000 people each year, mostly in developing regions. The rabies virus (Rabies lyssavirus) is a unique neurotropic virus that can invade the nervous system, escape host immune responses and produce a truly devastating nervous system disease. The molecular insights into rabies virus neuroinvasion and pathogenicity, reviewed in this paper, are described in a comprehensive overview. Structural and genomic characteristics of the virus, neuroinvasion mechanisms, and pathologic effects on the host are discussed. Additionally, we discuss the viral strategies they use to evade the host’s immune responses. We then review the challenges to current therapeutic approaches, including post exposure prophylaxis and vaccination. We conclude with suggestions of future research directed towards development of better prevention, diagnosis and treatment strategies for rabies.

Keywords:

Rabies Virus , neurotropic virus, pathogenicity

References

Fisher CR, Streicker DG, Schnell MJ. The spread and evolution of rabies virus: conquering new frontiers. Nat Rev Microbiol. 2018;16(4):241-55.

Khairullah AR, Kurniawan SC, Hasib A, Silaen OSM, Widodo A, Effendi MH, et al. Tracking lethal threat: in-depth review of rabies. Open Vet J. 2023;13(11):1385-99.

Rupprecht CE. Rhabdoviruses: rabies virus. Medical microbiology. 1996;4.

Davis BM, Rall GF, Schnell MJ. Everything You Always Wanted to Know About Rabies Virus (But Were Afraid to Ask). Annu Rev Virol. 2015;2(1):451-71.

Yu D, Jin R, Liu J, Zhang C, Duan C, Luo X, et al. Rabies Virus Infection Causes Pyroptosis of Neuronal Cells. International Journal of Molecular Sciences. 2024;25(11):5616.

Gelderblom HR. Structure and classification of viruses. Medical Microbiology 4th edition. 1996.

Garoff H, Hewson R, Opstelten DJ. Virus maturation by budding. Microbiol Mol Biol Rev. 1998;62(4):1171-90.

Dawood IRA. The Effect of Competitive Learning Strategy in Developing Mental visualization of some Basic Skills in Basketball for Students. JOURNAL OF SPORT SCIENCES. 2016;8(25).

Mebatsion T, Weiland F, Conzelmann KK. Matrix protein of rabies virus is responsible for the assembly and budding of bullet-shaped particles and interacts with the transmembrane spike glycoprotein G. J Virol. 1999;73(1):242-50.

Villanueva RA, Rouillé Y, Dubuisson J. Interactions between virus proteins and host cell membranes during the viral life cycle. Int Rev Cytol. 2005;245:171-244.

Dimitrov DS. Virus entry: molecular mechanisms and biomedical applications. Nat Rev Microbiol. 2004;2(2):109-22.

Wu H, Wang L, Tao X, Li H, Rayner S, Liang G, et al. Genetic diversity and molecular evolution of the rabies virus matrix protein gene in China. Infection, Genetics and Evolution. 2013;16:248-53.

Luo Y, Zhang Y, Liu X, Yang Y, Yang X, Zhang D, et al. Complete genome sequence of a highly virulent rabies virus isolated from a rabid pig in south China. J Virol. 2012;86(22):12454-5.

Dawood IRA, Tahseen TH. EXAMINATION OF THE USE OF PICTURE CARD TECHNOLOGY TO HELP ELEMENTARY SCHOOL STUDENTS DEVELOP THEIR BASKETBALL SKILLS. International Journal of Cognitive Neuroscience and Psychology. 2024;2(2):1-7.

Abdullah Salim Al K, Ali Mohammed A, Maarb Salih A, Alia Essam A, Dr. Reyam Naji A, Estabraq Mohammed A. THE ENVIRONMENTAL REALITY OF DESERTIFICATION IN IRAQ / 2022: A REVIEW ARTICLE. Open Access Repository. 2023;9(6):226-34.

Marston DA, Horton DL, Nunez J, Ellis RJ, Orton RJ, Johnson N, et al. Genetic analysis of a rabies virus host shift event reveals within-host viral dynamics in a new host. Virus Evol. 2017;3(2):vex038.

MOHAMMED M, Mousa D, Tareq Jafaar Al-Jindeel H, Al-Karawi S. Latent and reactivation Cytomegalovirus (CMV) infection can cause severe fetal sequelae despite pre-conceptional immunity.

Scott TP, Nel LH. Subversion of the Immune Response by Rabies Virus. Viruses. 2016;8(8).

Dietzschold B, Li J, Faber M, Schnell M. Concepts in the pathogenesis of rabies. Future Virol. 2008;3(5):481-90.

Baloul L, Lafon M. Apoptosis and rabies virus neuroinvasion. Biochimie. 2003;85(8):777-88.

Lafon M. Subversive neuroinvasive strategy of rabies virus. Emergence and Control of Zoonotic Viral Encephalitides. 2004:149-59.

Abdullah AM, Al-Karawi AS, Aswad OAK, Alubadi AE, Ati EM, Ajmi RN. Natural Reserves and Sustainable Development of AL-Tayeb Reserve/South Iraq: A Review Article. Global Scientific Review. 2023;16:29-37.

Hemachudha T, Ugolini G, Wacharapluesadee S, Sungkarat W, Shuangshoti S, Laothamatas J. Human rabies: neuropathogenesis, diagnosis, and management. The Lancet Neurology. 2013;12(5):498-513.

Wunner WH, Briggs DJ. Rabies in the 21st century. PLoS neglected tropical diseases. 2010;4(3):e591.

Lafon M. Rabies virus receptors. J Neurovirol. 2005;11(1):82-7.

White JM, Whittaker GR. Fusion of Enveloped Viruses in Endosomes. Traffic. 2016;17(6):593-614.

MacGibeny MA, Koyuncu OO, Wirblich C, Schnell MJ, Enquist LW. Retrograde axonal transport of rabies virus is unaffected by interferon treatment but blocked by emetine locally in axons. PLoS Pathog. 2018;14(7):e1007188.

Kellermann M, Scharte F, Hensel M. Manipulation of Host Cell Organelles by Intracellular Pathogens. Int J Mol Sci. 2021;22(12).

Ito N, Moseley GW, Sugiyama M. The importance of immune evasion in the pathogenesis of rabies virus. J Vet Med Sci. 2016;78(7):1089-98.

Bastos V, Pacheco V, Rodrigues ÉDL, Moraes CNS, Nóbile AL, Fonseca DLM, et al. Neuroimmunology of rabies: New insights into an ancient disease. Journal of Medical Virology. 2023;95(10):e29042.

Asaad LA, Al-Shimary AA, AL-Azzawi MA, Al-Karawi AS, Rasool KH. The Relationship between Renal Impairment and Specific Laboratory Markers: A Comprehensive Investigation Focusing on Athletes. Journal for ReAttach Therapy and Developmental Diversities. 2023;6(8s):452-8.

Li XQ, Sarmento L, Fu ZF. Degeneration of neuronal processes after infection with pathogenic, but not attenuated, rabies viruses. J Virol. 2005;79(15):10063-8.

Kim S, Larrous F, Varet H, Legendre R, Feige L, Dumas G, et al. Early Transcriptional Changes in Rabies Virus-Infected Neurons and Their Impact on Neuronal Functions. Front Microbiol. 2021;12:730892.

Wongchitrat P, Chanmee T, Govitrapong P. Molecular Mechanisms Associated with Neurodegeneration of Neurotropic Viral Infection. Mol Neurobiol. 2024;61(5):2881-903.

Abid FM, Al-Ajeeli FS, Al-Karawi AS, Rasool KH. Reversed phase HPLC determination of total homocysteine, cysteine, cysteinyl glycine, glutathione in plasma of epileptic patients. The American Journal of Medical Sciences and Pharmaceutical Research. 2023;5(07):34-45.

Mahmoud HQ, Mhana RS, Mohammed AA. Therapeutic options and management approach on thalassemia an overview. International Journal of Medical Science and Dental Health. 2024;10(01):17-28.

Mohammed AA, Mahmoud HQ, Mhana RS. ADVANCES IN THE DIAGNOSIS AND MANAGEMENT OF BREAST CANCER: A SYSTEMATIC REVIEW. World. 2023;2(6).

Farahtaj F, Alizadeh L, Gholami A, Tahamtan A, Shirian S, Fazeli M, et al. Natural Infection with Rabies Virus: A Histopathological and Immunohistochemical Study of Human Brains. Osong Public Health Res Perspect. 2019;10(1):6-11.

Al-Karawi AS, Kadhim AS. Exploring the role of autoantibodies in Iraqi females with polycystic ovary syndrome. 2024.

Ghosh S, Rana MS, Islam MK, Chowdhury S, Haider N, Kafi MAH, et al. Trends and clinico-epidemiological features of human rabies cases in Bangladesh 2006-2018. Sci Rep. 2020;10(1):2410.

Pulmanausahakul R, Li J, Schnell MJ, Dietzschold B. The glycoprotein and the matrix protein of rabies virus affect pathogenicity by regulating viral replication and facilitating cell-to-cell spread. J Virol. 2008;82(5):2330-8.

Ashraf HN, Uversky VN. Intrinsic Disorder in the Host Proteins Entrapped in Rabies Virus Particles. Viruses. 2024;16(6):916.

Kready HO, Mohammed M, Salem M, Al-Karwi AS. SCREENING AND DIAGNOSIS OF BETA-THALASSEMIA DEPENDING ON HBA2 AND BLOOD FILM IN BAGHDAD CITY. World. 2023;2(6).

Dhale PC, Mohammed AA, Al-Shimary AA, Shaikh AB, Kamble AA, Gaikwad SH, et al. Exploring Triazole-Based Co (Ii), Ni (Ii) and Cu (Ii) Complexes as Biologically Potent Molecules: Chemical Synthesis, Structural Elucidation and Molecular Docking Studies. Ni (Ii) and Cu (Ii) Complexes as Biologically Potent Molecules: Chemical Synthesis, Structural Elucidation and Molecular Docking Studies.

Zhang H, Huang J, Song Y, Liu X, Qian M, Huang P, et al. Regulation of innate immune responses by rabies virus. Animal Model Exp Med. 2022;5(5):418-29.

Kamble SA, Barale SS, Mohammed AA, Paymal SB, Naik NM, Sonawane KD. Structural insights into the potential binding sites of Cathepsin D using molecular modelling techniques. Amino Acids. 2024;56(1):33.

Appolinário CM, Allendorf SD, Peres MG, Ribeiro BD, Fonseca CR, Vicente AF, et al. Profile of Cytokines and Chemokines Triggered by Wild-Type Strains of Rabies Virus in Mice. Am J Trop Med Hyg. 2016;94(2):378-83.

Niu X, Wang H, Fu ZF. Role of chemokines in rabies pathogenesis and protection. Adv Virus Res. 2011;79:73-89.

Feige L, Sáenz-de-Santa-María I, Regnault B, Lavenir R, Lepelletier A, Halacu A, et al. Transcriptome Profile During Rabies Virus Infection: Identification of Human CXCL16 as a Potential New Viral Target. Frontiers in Cellular and Infection Microbiology. 2021;11.

Khamees HH, Mohammed AA, Hussein SAM, Ahmed MA, Raoof ASM. In-Silico study of Destabilizing Alzheimer’s Aβ42 Protofibrils with Curcumin. International Journal of Medical Science and Dental Health. 2024;10(05):76-84.

Vidy A, Chelbi-Alix M, Blondel D. Rabies virus P protein interacts with STAT1 and inhibits interferon signal transduction pathways. J Virol. 2005;79(22):14411-20.

Brzózka K, Finke S, Conzelmann KK. Inhibition of interferon signaling by rabies virus phosphoprotein P: activation-dependent binding of STAT1 and STAT2. J Virol. 2006;80(6):2675-83.