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CD4 Deficiency Causes Poliomyelitis and Axonal Blebbing in Murine Coronavirus-Induced Neuroinflammation.
Chakravarty, Debanjana; Saadi, Fareeha; Kundu, Soumya; Bose, Abhishek; Khan, Reas; Dine, Kimberly; Kenyon, Lawrence C; Shindler, Kenneth S; Das Sarma, Jayasri.
  • Chakravarty D; Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, India.
  • Saadi F; Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, India.
  • Kundu S; Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, India.
  • Bose A; Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, India.
  • Khan R; Department of Ophthalmology, University of Pennsylvania Scheie Eye Institute, Philadelphia, Pennsylvania, USA.
  • Dine K; Department of Ophthalmology, University of Pennsylvania Scheie Eye Institute, Philadelphia, Pennsylvania, USA.
  • Kenyon LC; Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
  • Shindler KS; Department of Ophthalmology, University of Pennsylvania Scheie Eye Institute, Philadelphia, Pennsylvania, USA Kenneth.Shindler@uphs.upenn.edu dassarmaj@iiserkol.ac.in.
  • Das Sarma J; Department of Neurology, University of Pennsylvania Scheie Eye Institute, Philadelphia, Pennsylvania, USA.
J Virol ; 94(14)2020 07 01.
Article in English | MEDLINE | ID: covidwho-823496
Semantic information from SemMedBD (by NLM)
1. T-Cell Surface Glycoprotein CD CAUSES C0032371
Subject
T-Cell Surface Glycoprotein CD
Predicate
CAUSES
Object
C0032371
2. Betacoronavirus PROCESS_OF Mus
Subject
Betacoronavirus
Predicate
PROCESS_OF
Object
Mus
3. Disease PROCESS_OF Mus
Subject
Disease
Predicate
PROCESS_OF
Object
Mus
4. Disease PROCESS_OF Rattus norvegicus
Subject
Disease
Predicate
PROCESS_OF
Object
Rattus norvegicus
5. Murine hepatitis virus PROCESS_OF Mus
Subject
Murine hepatitis virus
Predicate
PROCESS_OF
Object
Mus
6. disabling disease AFFECTS Young Adult
Subject
disabling disease
Predicate
AFFECTS
Object
Young Adult
7. Infiltration COEXISTS_WITH Multiple Sclerosis
Subject
Infiltration
Predicate
COEXISTS_WITH
Object
Multiple Sclerosis
8. Gene Amplification PROCESS_OF Nucleocapsid
Subject
Gene Amplification
Predicate
PROCESS_OF
Object
Nucleocapsid
9. Gangli LOCATION_OF C0021368
Subject
Gangli
Predicate
LOCATION_OF
Object
C0021368
10. Inflammation PROCESS_OF Mus
Subject
Inflammation
Predicate
PROCESS_OF
Object
Mus
11. Poliomyelitis PROCESS_OF Mus
Subject
Poliomyelitis
Predicate
PROCESS_OF
Object
Mus
12. Parenchyma PART_OF Brain
Subject
Parenchyma
Predicate
PART_OF
Object
Brain
13. macrophage PART_OF Mus
Subject
macrophage
Predicate
PART_OF
Object
Mus
14. CD4 Positive T Lymphocytes PART_OF Mus
Subject
CD4 Positive T Lymphocytes
Predicate
PART_OF
Object
Mus
15. Parenchyma LOCATION_OF Vacuolation
Subject
Parenchyma
Predicate
LOCATION_OF
Object
Vacuolation
16. Cerebral cortex LOCATION_OF Inflammation
Subject
Cerebral cortex
Predicate
LOCATION_OF
Object
Inflammation
17. T-Cell Surface Glycoprotein CD4, human|CD4 CAUSES Poliomyelitis
Subject
T-Cell Surface Glycoprotein CD4, human|CD4
Predicate
CAUSES
Object
Poliomyelitis
18. Betacoronavirus PROCESS_OF Mus
Subject
Betacoronavirus
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PROCESS_OF
Object
Mus
19. Disease PROCESS_OF Mus
Subject
Disease
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PROCESS_OF
Object
Mus
20. Disease PROCESS_OF Rattus norvegicus
Subject
Disease
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PROCESS_OF
Object
Rattus norvegicus
21. Murine hepatitis virus PROCESS_OF Mus
Subject
Murine hepatitis virus
Predicate
PROCESS_OF
Object
Mus
22. disabling disease AFFECTS Young Adult
Subject
disabling disease
Predicate
AFFECTS
Object
Young Adult
23. Infiltration COEXISTS_WITH Multiple Sclerosis
Subject
Infiltration
Predicate
COEXISTS_WITH
Object
Multiple Sclerosis
24. Gene Amplification PROCESS_OF Nucleocapsid
Subject
Gene Amplification
Predicate
PROCESS_OF
Object
Nucleocapsid
25. Ganglia, Spinal LOCATION_OF Inflammation
Subject
Ganglia, Spinal
Predicate
LOCATION_OF
Object
Inflammation
26. Inflammation PROCESS_OF Mus
Subject
Inflammation
Predicate
PROCESS_OF
Object
Mus
27. Poliomyelitis PROCESS_OF Mus
Subject
Poliomyelitis
Predicate
PROCESS_OF
Object
Mus
28. Parenchyma PART_OF Brain
Subject
Parenchyma
Predicate
PART_OF
Object
Brain
29. macrophage PART_OF Mus
Subject
macrophage
Predicate
PART_OF
Object
Mus
30. CD4 Positive T Lymphocytes PART_OF Mus
Subject
CD4 Positive T Lymphocytes
Predicate
PART_OF
Object
Mus
31. Parenchyma LOCATION_OF Vacuolation
Subject
Parenchyma
Predicate
LOCATION_OF
Object
Vacuolation
32. Cerebral cortex LOCATION_OF Inflammation
Subject
Cerebral cortex
Predicate
LOCATION_OF
Object
Inflammation
ABSTRACT
Mouse hepatitis virus (MHV) is a murine betacoronavirus (m-CoV) that causes a wide range of diseases in mice and rats, including hepatitis, enteritis, respiratory diseases, and encephalomyelitis in the central nervous system (CNS). MHV infection in mice provides an efficient cause-effect experimental model to understand the mechanisms of direct virus-induced neural-cell damage leading to demyelination and axonal loss, which are pathological features of multiple sclerosis (MS), the most common disabling neurological disease in young adults. Infiltration of T lymphocytes, activation of microglia, and their interplay are the primary pathophysiological events leading to disruption of the myelin sheath in MS. However, there is emerging evidence supporting gray matter involvement and degeneration in MS. The investigation of T cell function in the pathogenesis of deep gray matter damage is necessary. Here, we employed RSA59 (an isogenic recombinant strain of MHV-A59)-induced experimental neuroinflammation model to compare the disease in CD4-/- mice with that in CD4+/+ mice at days 5, 10, 15, and 30 postinfection (p.i.). Viral titer estimation, nucleocapsid gene amplification, and viral antinucleocapsid staining confirmed enhanced replication of the virions in the absence of functional CD4+ T cells in the brain. Histopathological analyses showed elevated susceptibility of CD4-/- mice to axonal degeneration in the CNS, with augmented progression of acute poliomyelitis and dorsal root ganglionic inflammation rarely observed in CD4+/+ mice. Depletion of CD4+ T cells showed unique pathological bulbar vacuolation in the brain parenchyma of infected mice with persistent CD11b+ microglia/macrophages in the inflamed regions on day 30 p.i. In summary, the current study suggests that CD4+ T cells are critical for controlling acute-stage poliomyelitis (gray matter inflammation), chronic axonal degeneration, and inflammatory demyelination due to loss of protective antiviral host immunity.IMPORTANCE The current trend in CNS disease biology is to attempt to understand the neural-cell-immune interaction to investigate the underlying mechanism of neuroinflammation, rather than focusing on peripheral immune activation. Most studies in MS are targeted toward understanding the involvement of CNS white matter. However, the importance of gray matter damage has become critical in understanding the long-term progressive neurological disorder. Our study highlights the importance of CD4+ T cells in safeguarding neurons against axonal blebbing and poliomyelitis from murine betacoronavirus-induced neuroinflammation. Current knowledge of the mechanisms that lead to gray matter damage in MS is limited, because the most widely used animal model, experimental autoimmune encephalomyelitis (EAE), does not present this aspect of the disease. Our results, therefore, add to the existing limited knowledge in the field. We also show that the microglia, though important for the initiation of neuroinflammation, cannot establish a protective host immune response without the help of CD4+ T cells.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Poliomyelitis / Axons / CD4 Antigens / Coronavirus Infections / Murine hepatitis virus Limits: Animals Language: English Year: 2020 Document Type: Article Affiliation country: JVI.00548-20

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Poliomyelitis / Axons / CD4 Antigens / Coronavirus Infections / Murine hepatitis virus Limits: Animals Language: English Year: 2020 Document Type: Article Affiliation country: JVI.00548-20