The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 17 January 2006 doi:10.1084/jem.20051970
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 1, 35-40
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 631K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Glass, W. G.
Right arrow Articles by Murphy, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Glass, W. G.
Right arrow Articles by Murphy, P. M.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*OMIM
*Protein*UniGene
Medline Plus Health Information
*West Nile Virus
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

BRIEF DEFINITIVE REPORT

 CCR5 deficiency increases risk of symptomatic West Nile virus infection

William G. Glass1, David H. McDermott1, Jean K. Lim1, Sudkamon Lekhong2, Shuk Fong Yu2, William A. Frank3, John Pape4, Ronald C. Cheshier2, and Philip M. Murphy1

1 Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
2 Bureau of State Laboratory Services and 3 Bureau of Epidemiology and Disease Control Services, Arizona Department of Health Services, Phoenix, AZ 85007
4 Colorado Department of Public Health and Environment, Denver, CO 80246

CORRESPONDENCE Philip M. Murphy: pmm{at}nih.gov

West Nile virus (WNV) is a reemerging pathogen that causes fatal encephalitis in several species, including mouse and human. Recently, we showed that the chemokine receptor CCR5 is critical for survival of mice infected with WNV, acting at the level of leukocyte trafficking to the brain. To test whether this receptor is also protective in man, we determined the frequency of CCR5{Delta}32, a defective CCR5 allele found predominantly in Caucasians, in two independent cohorts of patients, one from Arizona and the other from Colorado, who had laboratory-confirmed, symptomatic WNV infection. The distribution of CCR5{Delta}32 in a control population of healthy United States Caucasian random blood donors was in Hardy-Weinberg equilibrium and CCR5{Delta}32 homozygotes represented 1.0% of the total group (n = 1,318). In contrast, CCR5{Delta}32 homozygotes represented 4.2% of Caucasians in the Arizona cohort (odds ratios [OR] = 4.4 [95% confidence interval [CI], 1.6–11.8], P = 0.0013) and 8.3% of Caucasians in the Colorado cohort (OR = 9.1 [95% CI, 3.4–24.8], P < 0.0001). CCR5{Delta}32 homozygosity was significantly associated with fatal outcome in the Arizona cohort (OR = 13.2 [95% CI, 1.9–89.9], P = 0.03). We conclude that CCR5 mediates resistance to symptomatic WNV infection. Because CCR5 is also the major HIV coreceptor, these findings have important implications for the safety of CCR5-blocking agents under development for HIV/AIDS.

W.G. Glass's present address is Centocor Global R&D, Infectious Diseases, Radnor, PA 19087.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

CCR5 thwarts West Nile virus
Heather L. Van Epps
J. Exp. Med. 2006 203: 4a. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS