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Involvement of natural killer cells in coxsackievirus B3-induced murine myocarditis
Abstract:
The role of natural killer cells in the temporal development of coxsackievirus B3-induced myocarditis in adolescent CD-1 male mice was examined. Inoculation of purified CVB3m induced maximum NK cell activity in the splenic populations at 3 days postinoculation (p.i.) as assessed by lysis of YAC-1 cells; maximum virus titers in heart tissues were also found at day 3 p.i. Mice depleted of NK cells after injection of anti-asialo GM1 antiserum i.v. had decreased NK cell activity, increased CVB3m titers in heart tissues, and exacerbated myocarditis. Although lesion number was not increased in heart tissues of the latter mice, lesions in these mice exhibited increased myocyte degeneration and dystrophic calcification above that found in lesions of mice inoculated with CVB3m only. No alteration in interferon titers were observed in CVB3m-infected mice treated with anti-asialo GM1 antiserum as compared with normal CVB3m-infected mice. Measurements of splenic NK cell activity in mice inoculated with doses of 10(2) to 10(8) PFU of CVB3m per mouse or UV-irradiated virus suggest that replication of CVB3m is required for NK cell activation. An amyocarditic variant of CVB3m (ts5R) was shown to replicate in heart tissues and to elicit NK cell activity comparable to that elicited by CVB3m. Therefore, the data suggest that NK cell activation depends on virus replication and that these cells provide some protection against CVB3m-induced myocarditis by limiting virus replication in heart tissues.
Insights
Natural killer (NK) cells are crucial in fighting coxsackievirus B3 (CVB3) myocarditis. Depleting NK cells worsens heart inflammation and viral load, indicating their protective role against this viral heart infection.
Area of Science:
- Immunology
- Virology
- Cardiovascular Research
Background:
- Myocarditis is inflammation of the heart muscle, often caused by viral infections like coxsackievirus B3 (CVB3).
- Natural killer (NK) cells are a type of immune cell known for their role in antiviral defense.
Purpose of the Study:
- To investigate the role of NK cells in the development of CVB3-induced myocarditis.
- To determine if NK cell activation is dependent on viral replication and if NK cells offer protection against CVB3 myocarditis.
Main Methods:
- Mice were inoculated with CVB3, and NK cell activity was measured over time.
- NK cells were depleted using anti-asialo GM1 antiserum to assess their impact on myocarditis severity and viral titers.
- Different doses of CVB3 and a non-myocarditic variant were used to study NK cell activation.
Main Results:
- NK cell activity peaked at 3 days post-inoculation, coinciding with peak viral titers in the heart.
- Mice depleted of NK cells showed increased viral loads, exacerbated myocarditis with greater myocyte damage, but similar lesion numbers.
- NK cell activation was dependent on CVB3 replication, and an amyocarditic viral variant also elicited NK cell activity.
Conclusions:
- NK cell activation is triggered by coxsackievirus B3 replication.
- NK cells play a protective role in CVB3-induced myocarditis by limiting viral replication in the heart.
- NK cell depletion leads to more severe heart damage despite similar lesion formation.