4.4 Article

An intermediate dose of LCMV clone 13 causes prolonged morbidity that is maintained by CD4+T cells

Journal

VIROLOGY
Volume 425, Issue 2, Pages 122-132

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2012.01.005

Keywords

Virus dose; LCMV; cl-13; Persistent infection; CD4+T cells; Wasting; Cachexia; TNF alpha; IFN gamma

Categories

Funding

  1. US National Institutes of Health [R00 AI076346-01]
  2. Harvey V. Berneking Living Trust
  3. National Center for Research Resources (NCRR) [UL1 RR024131]

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Wasting is a sign of various underlying disorders and is a common feature of cancer, sepsis, and AIDS. We have developed an in vivo model to study the various stages of wasting following infection of mice with lymphocytic choriomeningitis virus cl-13. Using this model we have identified four distinct stages of wasting and have discovered that all stages occur in the different groups of mice regardless of whether the virus is cleared or persists. However, the degree and extent of wasting vary between groups of mice, depending upon the dose of virus administered. Blocking IFN gamma or TNF alpha, which are believed to take part in the wasting process, did not affect the wasting state. Finally, we found that CD4+ T cells control the maintenance stage of wasting. We believe this model will be useful in studying the regulation of wasting during a persistent viral infection, hopefully leading to improved therapies to ameliorate the disorder. (C) 2012 Elsevier Inc. All rights reserved.

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