NDLI: Coxsackievirus B3-Induced Myocarditis

Content Provider	PubMed Central
Author	Gebhard, John R. Perry, Christopher M. Harkins, Stephanie Lane, Thomas Mena, Ignacio Asensio, Valérie C. Campbell, Iain L. Whitton, J. Lindsay
Abstract	Viral myocarditis is remarkably common, being detected in approximately 1% of unselected asymptomatic individuals. Many cases are attributable to enteroviral infection, and in particular to coxsackievirus B3. The underlying pathogenesis is controversial, but most studies admit the important immunopathological role of infiltrating CD8+ (cytotoxic) T lymphocytes (CTLs). We have previously shown that CTLs play conflicting roles in coxsackievirus B (CVB) myocarditis; they assist in controlling virus replication, but also are instrumental in causing the extensive inflammatory disease, which often results in severe myocardial scarring. A role for perforin, the major CTL cytolytic protein, in CVB myocarditis has been suggested, but never proven. In the present study we use perforin knockout (PKO) mice to show that perforin plays a major role in CVB infection; in broad terms, perforin is important in immunopathology, but not in CVB clearance. For example, PKO mice are better able to withstand a normally lethal dose of CVB (100% survival of PKO mice compared with 90% death in +/+ littermates). In addition, PKO mice given a nonlethal dose of CVB develop only a mild myocarditis, whereas their perforin+ littermates have extensive myocardial lesions. The myocarditis in PKO mice resolves more quickly, and these mice show minimal histological sequelae; in contrast, late in disease the perforin+ mice develop severe myocardial fibrosis. PKO mice, despite lacking this major CTL effector function, can control the infection and eradicate the virus; growth kinetics and peak CVB titers are indistinguishable in PKO and perforin+ mice. Therefore, the immunopathological and antiviral effects of CTLs can be uncoupled by ablation of perforin; this offers a promising target for therapy of myocarditis. Furthermore, we evaluate the possible roles of apoptosis, and of chemokine expression, in CVB infection. In perforin+ mice, apoptotic cells are detected within the inflammatory infiltrate, whereas in their PKO counterparts, apoptotic myocyte nuclei are seen. Chemokine expression in both PKO and perforin+ mice precedes and parallels the course of myocarditis. Several chemokines are detectable earlier in PKO mice than in perforin+ mice, but PKO mice show reduced peak levels, and chemokine expression decays sooner. In particular, MIP-1α expression is barely detectable at any time point in PKO mice, but it is readily identified in perforin+ animals, peaking just before the time of maximal myocarditis; this is particularly interesting, given that MIP-1α knockout mice are resistant to CVB myocarditis, but remain able to control viral infection. Thus, the chemokine pathway offers a second route of intervention to diminish myocarditis and its sequelae, while permitting the host to eradicate the virus.
Related Links	http://dx.doi.org/10.1016/s0002-9440(10)65585-x
Ending Page	428
Page Count	12
Starting Page	417
File Format	PDF
ISSN	00029440
e-ISSN	15252191
Journal	The American Journal of Pathology
Issue Number	2
Volume Number	153
Language	English
Publisher	American Society for Investigative Pathology
Publisher Date	1998-08-01
Access Restriction	Open
Rights Holder	American Society for Investigative Pathology
Subject Keyword	Pathology and Forensic Medicine Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pathology and Forensic Medicine

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Progressive interstitial collagen deposition in Coxsackievirus B3-induced murine myocarditis.

Extracellular matrix remodelling after coxsackievirus B3-induced murine myocarditis.

In situ immune autoradiographic identification of cells in heart tissues of mice with coxsackievirus B3-induced myocarditis.

Characterization of a murine model of myocarditis induced by a reactivated coxsackievirus B3.

Coxsackievirus B3-induced myocarditis. Autoimmunity is L3T4+ T helper cell and IL-2 independent in BALB/c mice.

Coxsackievirus B3-induced myocarditis. Characterization of stable attenuated variants that protect against infection with the cardiovirulent wild-type strain.

Susceptibility to Coxsackievirus B3-induced chronic myocarditis maps near the murine Tcr alpha and Myhc alpha loci on chromosome 14.

Coxsackievirus B3 sequences in the myocardium of fatal cases in a cluster of acute myocarditis in Greece

IL-21R Expression on CD8+T Cells Promotes CD8+ T cell Activation in Coxsackievirus B3 Induced Myocarditis

Coxsackievirus B3-Induced Myocarditis

Similar Documents

Progressive interstitial collagen deposition in Coxsackievirus B3-induced murine myocarditis.

Extracellular matrix remodelling after coxsackievirus B3-induced murine myocarditis.

In situ immune autoradiographic identification of cells in heart tissues of mice with coxsackievirus B3-induced myocarditis.

Characterization of a murine model of myocarditis induced by a reactivated coxsackievirus B3.

Coxsackievirus B3-induced myocarditis. Autoimmunity is L3T4+ T helper cell and IL-2 independent in BALB/c mice.

Coxsackievirus B3-induced myocarditis. Characterization of stable attenuated variants that protect against infection with the cardiovirulent wild-type strain.

Susceptibility to Coxsackievirus B3-induced chronic myocarditis maps near the murine Tcr alpha and Myhc alpha loci on chromosome 14.

Coxsackievirus B3 sequences in the myocardium of fatal cases in a cluster of acute myocarditis in Greece

IL-21R Expression on CD8+T Cells Promotes CD8+ T cell Activation in Coxsackievirus B3 Induced Myocarditis

Coxsackievirus B3-Induced Myocarditis