Pathogenesis of murine gammaherpesvirus-68 infection in interleukin-6-deficient mice.
Murine gammaherpesvirus-68 (MHV-68) induces high levels of interleukin (IL)-6 production in both naive and primed lymphocyte populations. Mice that are homozygous (-/-) for deletion of the IL-6 gene were used to investigate the role of this cytokine in MHV-68 infection. The results showed that IL-6 is not essential for clearance of infectious MHV-68 from the lung or for the establishment, or control, of viral latency. Both IL-6 +/+ and -/- mice eliminated replicating virus from the respiratory tract within 15 days of infection, and their lungs remained clear of infectious virus for >/=150 days. Interestingly, the IL-6 -/- mice had both increased numbers of natural killer (NK)1.1+ cells and higher levels of NK cell activity than the +/+ controls at 10-15 days after infection. However, there was no difference in the cytotoxic T cell activity between the two groups of mice. Levels of latent virus were comparable in IL-6 +/+ and -/- mice over the time course studied. Furthermore, analysis of the numbers, types, and activation status of the various leukocyte subsets (other than NK cells) in the bronchoalveolar lavage population, lymph nodes, and spleens of +/+ and -/- mice revealed no striking differences. Apart from the expected lack of IL-6, cytokine profiles were not dramatically altered in IL-6 -/- mice. Thus, there is no evidence for an obligatory role for IL-6 in T cell activation during infection with MHV-68.
Sarawar
S R
SR
St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, Tennessee, 38105, USA.
Brooks
J W
JW
Cardin
R D
RD
Mehrpooya
M
M
Doherty
P C
PC
D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018142:Gammaherpesvirinae / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D006566:Herpesviridae Infections / Q000209:etiology* / Q000276:immunology / Q000821:virology; D007249:Inflammation / Q000209:etiology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D008168:Lung / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D014779:Virus Replication
D016207:Cytokines; D017931:DNA Primers; D015850:Interleukin-6