TNFα, interferon, and stress response induction as a function of age- related susceptibility to fatal sindbis virus infection of mice

Joanne Trgovcich, Judith Aronson, J. Charles Eldridge, Robert E. Johnston

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The age-related acquisition of resistance to fatal Sindbis virus infection was examined using a molecularly cloned laboratory strain of the AR339 isolate designated TRSB. TRSB caused 100% mortality in mice up to 5 days of age. Resistance to fatal infection developed abruptly between 5 and 9 days of age. Lethal Sindbis virus infection of mice inoculated at 4 days of age was characterized by high levels of virus replication, induction of high levels of interferon-α/β and TNF-α and severe thymic involution indicative of a systemic stress response. These changes correlated with predominantly noninflammatory lesions. In contrast, TRSB infection of older mice was characterized by survival, more limited virus replication, reduced cytokine induction, and the development of inflammatory responses leading to encephalitis, myositis, and myocarditis. Previous studies utilized infections of neonatal mice with TRSB and an attenuated mutant of TRSB to compare fatal and nonfatal Sindbis infection (Trgovcich et al., 1996. Virology 224, 73-83). The experiments reported here utilize mouse age at the time of infection to create conditions for examination of fatal and nonfatal TRSB infections. Both experiments suggest that fatal infection is associated with a shock-like syndrome and little or no inflammatory pathology, while survival is correlated with greatly reduced cytokine levels and inflammatory lesions.

Original languageEnglish (US)
Pages (from-to)339-348
Number of pages10
JournalVirology
Volume263
Issue number2
DOIs
StatePublished - Oct 25 1999
Externally publishedYes

Fingerprint

Sindbis Virus
Virus Diseases
Interferons
Infection
Virus Replication
Cytokines
Virus Activation
Virology
Myositis
Myocarditis
Encephalitis
Shock
Pathology
Mortality

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

TNFα, interferon, and stress response induction as a function of age- related susceptibility to fatal sindbis virus infection of mice. / Trgovcich, Joanne; Aronson, Judith; Eldridge, J. Charles; Johnston, Robert E.

In: Virology, Vol. 263, No. 2, 25.10.1999, p. 339-348.

Research output: Contribution to journalArticle

Trgovcich, Joanne ; Aronson, Judith ; Eldridge, J. Charles ; Johnston, Robert E. / TNFα, interferon, and stress response induction as a function of age- related susceptibility to fatal sindbis virus infection of mice. In: Virology. 1999 ; Vol. 263, No. 2. pp. 339-348.
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