The Immune Escape Strategy of Rabies Virus and Its Pathogenicity Mechanisms
In contrast to most other rhabdoviruses, which spread by insect vectors, the rabies virus (RABV) is a very unusual member of the Rhabdoviridae family, since it has evolved to be fully adapted to warm-blooded hosts and spread directly between them. There are differences in the immune responses to lab...
Saved in:
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/16/11/1774 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850227817627779072 |
|---|---|
| author | Abraha Bahlbi Kiflu |
| author_facet | Abraha Bahlbi Kiflu |
| author_sort | Abraha Bahlbi Kiflu |
| collection | DOAJ |
| description | In contrast to most other rhabdoviruses, which spread by insect vectors, the rabies virus (RABV) is a very unusual member of the Rhabdoviridae family, since it has evolved to be fully adapted to warm-blooded hosts and spread directly between them. There are differences in the immune responses to laboratory-attenuated RABV and wild-type rabies virus infections. Various investigations showed that whilst laboratory-attenuated RABV elicits an innate immune response, wild-type RABV evades detection. Pathogenic RABV infection bypasses immune response by antagonizing interferon induction, which prevents downstream signal activation and impairs antiviral proteins and inflammatory cytokines production that could eliminate the virus. On the contrary, non-pathogenic RABV infection leads to immune activation and suppresses the disease. Apart from that, through recruiting leukocytes into the central nervous system (CNS) and enhancing the blood–brain barrier (BBB) permeability, which are vital factors for viral clearance and protection, cytokines/chemokines released during RABV infection play a critical role in suppressing the disease. Furthermore, early apoptosis of neural cells limit replication and spread of avirulent RABV infection, but street RABV strains infection cause delayed apoptosis that help them spread further to healthy cells and circumvent early immune exposure. Similarly, a cellular regulation mechanism called autophagy eliminates unused or damaged cytoplasmic materials and destroy microbes by delivering them to the lysosomes as part of a nonspecific immune defense mechanism. Infection with laboratory fixed RABV strains lead to complete autophagy and the viruses are eliminated. But incomplete autophagy during pathogenic RABV infection failed to destroy the viruses and might aid the virus in dodging detection by antigen-presenting cells, which could otherwise elicit adaptive immune activation. Pathogenic RABV P and M proteins, as well as high concentration of nitric oxide, which is produced during rabies virus infection, inhibits activities of mitochondrial proteins, which triggers the generation of reactive oxygen species, resulting in oxidative stress, contributing to mitochondrial malfunction and, finally, neuron process degeneration. |
| format | Article |
| id | doaj-art-29e94183df9740d5b328c065ae9bde32 |
| institution | OA Journals |
| issn | 1999-4915 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-29e94183df9740d5b328c065ae9bde322025-08-20T02:04:43ZengMDPI AGViruses1999-49152024-11-011611177410.3390/v16111774The Immune Escape Strategy of Rabies Virus and Its Pathogenicity MechanismsAbraha Bahlbi Kiflu0State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530004, ChinaIn contrast to most other rhabdoviruses, which spread by insect vectors, the rabies virus (RABV) is a very unusual member of the Rhabdoviridae family, since it has evolved to be fully adapted to warm-blooded hosts and spread directly between them. There are differences in the immune responses to laboratory-attenuated RABV and wild-type rabies virus infections. Various investigations showed that whilst laboratory-attenuated RABV elicits an innate immune response, wild-type RABV evades detection. Pathogenic RABV infection bypasses immune response by antagonizing interferon induction, which prevents downstream signal activation and impairs antiviral proteins and inflammatory cytokines production that could eliminate the virus. On the contrary, non-pathogenic RABV infection leads to immune activation and suppresses the disease. Apart from that, through recruiting leukocytes into the central nervous system (CNS) and enhancing the blood–brain barrier (BBB) permeability, which are vital factors for viral clearance and protection, cytokines/chemokines released during RABV infection play a critical role in suppressing the disease. Furthermore, early apoptosis of neural cells limit replication and spread of avirulent RABV infection, but street RABV strains infection cause delayed apoptosis that help them spread further to healthy cells and circumvent early immune exposure. Similarly, a cellular regulation mechanism called autophagy eliminates unused or damaged cytoplasmic materials and destroy microbes by delivering them to the lysosomes as part of a nonspecific immune defense mechanism. Infection with laboratory fixed RABV strains lead to complete autophagy and the viruses are eliminated. But incomplete autophagy during pathogenic RABV infection failed to destroy the viruses and might aid the virus in dodging detection by antigen-presenting cells, which could otherwise elicit adaptive immune activation. Pathogenic RABV P and M proteins, as well as high concentration of nitric oxide, which is produced during rabies virus infection, inhibits activities of mitochondrial proteins, which triggers the generation of reactive oxygen species, resulting in oxidative stress, contributing to mitochondrial malfunction and, finally, neuron process degeneration.https://www.mdpi.com/1999-4915/16/11/1774RABVimmune evasionIFN-α/βcytkines/chemokinesBBB permeabilityapoptosis |
| spellingShingle | Abraha Bahlbi Kiflu The Immune Escape Strategy of Rabies Virus and Its Pathogenicity Mechanisms Viruses RABV immune evasion IFN-α/β cytkines/chemokines BBB permeability apoptosis |
| title | The Immune Escape Strategy of Rabies Virus and Its Pathogenicity Mechanisms |
| title_full | The Immune Escape Strategy of Rabies Virus and Its Pathogenicity Mechanisms |
| title_fullStr | The Immune Escape Strategy of Rabies Virus and Its Pathogenicity Mechanisms |
| title_full_unstemmed | The Immune Escape Strategy of Rabies Virus and Its Pathogenicity Mechanisms |
| title_short | The Immune Escape Strategy of Rabies Virus and Its Pathogenicity Mechanisms |
| title_sort | immune escape strategy of rabies virus and its pathogenicity mechanisms |
| topic | RABV immune evasion IFN-α/β cytkines/chemokines BBB permeability apoptosis |
| url | https://www.mdpi.com/1999-4915/16/11/1774 |
| work_keys_str_mv | AT abrahabahlbikiflu theimmuneescapestrategyofrabiesvirusanditspathogenicitymechanisms AT abrahabahlbikiflu immuneescapestrategyofrabiesvirusanditspathogenicitymechanisms |