Exhaustion of type I interferon response following an acute viral infection.
Viral infections often cause a period of heightened susceptibility to a secondary infection but the cause of this phenomenon is unknown. We found that a primary viral infection in mice rapidly triggers an IFN-I-dependent partial activation state in the majority of B and T lymphocytes, which reverts to a resting phenotype within 5 days. When a secondary infection with an unrelated virus occurred 5 to 9 days after the primary infection, no recurrence of marked activation of lymphocytes was observed. This was not due to an inherent inability of the previously activated cells to undergo renewed partial activation, because they responded when challenged with virus after transfer into "naive" recipients. Instead, the failure to respond optimally resided in the original host's incapacity to mount an IFN-I response to the secondary infection during this time period. Thus, transient immunosuppression through exhaustion of IFN-I production during an acute viral infection creates a time period of enhanced susceptibility to secondary infection.
Alsharifi
Mohammed
M
Division of Immunology and Genetics, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia.
Regner
Matthias
M
Blanden
Robert
R
Lobigs
Mario
M
Lee
Eva
E
Koskinen
Aulikki
A
Müllbacher
Arno
A
D000208:Acute Disease; D000256:Adenoviridae / Q000502:physiology; D000257:Adenoviridae Infections / Q000276:immunology / Q000821:virology; D018354:Alphavirus Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015415:Biomarkers; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004481:Ectromelia virus / Q000472:pathogenicity; D004482:Ectromelia, Infectious / Q000276:immunology / Q000821:virology; D007370:Interferon Type I / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D012672:Semliki forest virus / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology* / Q000378:metabolism* / Q000821:virology
D015415:Biomarkers; D007370:Interferon Type I