Toll-like receptor 4 mediates blood-brain barrier permeability and disease in C3H mice during Venezuelan equine encephalitis virus infection: Venezuelan equine encephalitis virus and toll-like receptor 4
| Autor: | Bradley S. Hollidge, Courtney A. Cohen, Connie S. Schmaljohn, Justice Akuoku Frimpong, Catherine V. Badger, John M. Dye |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
animal structures viruses Immunology toll-like receptor 4 Alphavirus Disease Infectious and parasitic diseases RC109-216 tlr4 medicine.disease_cause Blood–brain barrier Microbiology venezuelan equine encephalitis virus 03 medical and health sciences parasitic diseases medicine 030304 developmental biology veev 0303 health sciences Toll-like receptor biology 030306 microbiology food and beverages virus diseases blood-brain barrier biology.organism_classification medicine.disease Virology Infectious Diseases medicine.anatomical_structure Venezuelan equine encephalitis virus TLR4 Parasitology Blood brain barrier permeability Encephalitis |
| Zdroj: | Virulence, Vol 12, Iss 1, Pp 430-443 (2021) |
| ISSN: | 2150-5608 2150-5594 |
| Popis: | Venezuelan equine encephalitis virus (VEEV) is an encephalitic alphavirus that can cause debilitating, acute febrile illness and potentially result in encephalitis. Currently, there are no FDA-licensed vaccines or specific therapeutics for VEEV. Previous studies have demonstrated that VEEV infection results in increased blood-brain barrier (BBB) permeability that is mediated by matrix metalloproteinases (MMPs). Furthermore, after subarachnoid hemorrhage in mice, MMP-9 is upregulated in the brain and mediates BBB permeability in a toll-like receptor 4 (TLR4)-dependent manner. Here, we demonstrate that disease in C3H mice during VEEV TC-83 infection is dependent on TLR4 because intranasal infection of C3H/HeN (TLR4WT) mice with VEEV TC-83 resulted in mortality as opposed to survival of TLR4-defective C3H/HeJ (TLR4mut) mice. In addition, BBB permeability was induced to a lesser extent in TLR4mut mice compared with TLR4WT mice during VEEV TC-83 infection as determined by sodium fluorescein and fluorescently-conjugated dextran extravasation. Moreover, MMP-9, MMP-2, ICAM-1, CCL2 and IFN-γ were all induced to significantly lower levels in the brains of infected TLR4mut mice compared with infected TLR4WT mice despite the absence of significantly different viral titers or immune cell populations in the brains of infected TLR4WT and TLR4mut mice. These data demonstrate the critical role of TLR4 in mediating BBB permeability and disease in C3H mice during VEEV TC-83 infection, which suggests that TLR4 is a potential target for the development of therapeutics for VEEV. |
| Databáze: | OpenAIRE |
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