scholarly journals CCR5 deficiency increases risk of symptomatic West Nile virus infection

2006 ◽  
Vol 203 (1) ◽  
pp. 35-40 ◽  
Author(s):  
William G. Glass ◽  
David H. McDermott ◽  
Jean K. Lim ◽  
Sudkamon Lekhong ◽  
Shuk Fong Yu ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Blood Donors ◽  
Fatal Outcome ◽  
West Nile Virus Infection ◽  
Leukocyte Trafficking ◽  
West Nile ◽  
Chemokine Receptor Ccr5 ◽  
Hardy Weinberg Equilibrium ◽  
The Brain ◽  
Receptor Ccr5

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 CCR5Δ32, 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 CCR5Δ32 in a control population of healthy United States Caucasian random blood donors was in Hardy-Weinberg equilibrium and CCR5Δ32 homozygotes represented 1.0% of the total group (n = 1,318). In contrast, CCR5Δ32 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). CCR5Δ32 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.

scholarly journals Chemokine receptor CCR5 promotes leukocyte trafficking to the brain and survival in West Nile virus infection

2005 ◽  
Vol 202 (8) ◽  
pp. 1087-1098 ◽  
Author(s):  
William G. Glass ◽  
Jean K. Lim ◽  
Rushina Cholera ◽  
Alexander G. Pletnev ◽  
Ji-Liang Gao ◽  
...  
Keyword(s):  
T Cells ◽  
West Nile Virus ◽  
Chemokine Receptor ◽  
Cd8 T Cells ◽  
West Nile Virus Infection ◽  
West Nile ◽  
Leukocyte Accumulation ◽  
Chemokine Receptor Ccr5 ◽  
The Brain ◽  
Receptor Ccr5

The molecular immunopathogenesis of West Nile virus (WNV) infection is poorly understood. Here, we characterize a mouse model for WNV using a subcutaneous route of infection and delineate leukocyte subsets and immunoregulatory factors present in the brains of infected mice. Central nervous system (CNS) expression of the chemokine receptor CCR5 and its ligand CCL5 was prominently up-regulated by WNV, and this was associated with CNS infiltration of CD4+ and CD8+ T cells, NK1.1+ cells and macrophages expressing the receptor. The significance of CCR5 in pathogenesis was established by mortality studies in which infection of CCR5−/− mice was rapidly and uniformly fatal. In the brain, WNV-infected CCR5−/− mice had increased viral burden but markedly reduced NK1.1+ cells, macrophages, and CD4+ and CD8+ T cells compared with WNV-infected CCR5+/+ mice. Adoptive transfer of splenocytes from WNV-infected CCR5+/+ mice into infected CCR5−/− mice increased leukocyte accumulation in the CNS compared with transfer of splenocytes from infected CCR5−/− mice into infected CCR5−/− mice, and increased survival to 60%, the same as in infected CCR5+/+ control mice. We conclude that CCR5 is a critical antiviral and survival determinant in WNV infection of mice that acts by regulating trafficking of leukocytes to the infected brain.

scholarly journals Interferon-λ restricts West Nile virus neuroinvasion by tightening the blood-brain barrier

2015 ◽  
Vol 7 (284) ◽  
pp. 284ra59-284ra59 ◽  
Author(s):  
Helen M. Lazear ◽  
Brian P. Daniels ◽  
Amelia K. Pinto ◽  
Albert C. Huang ◽  
Sarah C. Vick ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Blood Brain Barrier ◽  
West Nile Virus Infection ◽  
Antiviral Effect ◽  
Brain Barrier ◽  
West Nile ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
The Brain ◽  
Interferon Λ

Although interferon-λ [also known as type III interferon or interleukin-28 (IL-28)/IL-29] restricts infection by several viruses, its inhibitory mechanism has remained uncertain. We used recombinant interferon-λ and mice lacking the interferon-λ receptor (IFNLR1) to evaluate the effect of interferon-λ on infection with West Nile virus, an encephalitic flavivirus. Cell culture studies in mouse keratinocytes and dendritic cells showed no direct antiviral effect of exogenous interferon-λ, even though expression of interferon-stimulated genes was induced. We observed no differences in West Nile virus burden between wild-type and Ifnlr1−/− mice in the draining lymph nodes, spleen, or blood. We detected increased West Nile virus infection in the brain and spinal cord of Ifnlr1−/− mice, yet this was not associated with a direct antiviral effect in mouse neurons. Instead, we observed an increase in blood-brain barrier permeability in Ifnlr1−/− mice. Treatment of mice with pegylated interferon-λ2 resulted in decreased blood-brain barrier permeability, reduced West Nile virus infection in the brain without affecting viremia, and improved survival against lethal virus challenge. An in vitro model of the blood-brain barrier showed that interferon-λ signaling in mouse brain microvascular endothelial cells increased transendothelial electrical resistance, decreased virus movement across the barrier, and modulated tight junction protein localization in a protein synthesis– and signal transducer and activator of transcription 1 (STAT1)–independent manner. Our data establish an indirect antiviral function of interferon-λ in which noncanonical signaling through IFNLR1 tightens the blood-brain barrier and restricts viral neuroinvasion and pathogenesis.

West Nile virus infection in blood donors in the New York City area during the 2010 seasonal epidemic

Transfusion ◽  
2012 ◽  
Vol 52 (12) ◽  
pp. 2664-2670 ◽  
Author(s):  
Richard O. Francis ◽  
Donna Strauss ◽  
Joan Dunn Williams ◽  
Shavonne Whaley ◽  
Beth H. Shaz
Keyword(s):  
New York ◽  
New York City ◽  
West Nile Virus ◽  
Virus Infection ◽  
York City ◽  
Blood Donors ◽  
West Nile Virus Infection ◽  
West Nile ◽  
City Area ◽  
Seasonal Epidemic

No evidence of West Nile virus infection in Dutch blood donors

Vox Sanguinis ◽  
2006 ◽  
Vol 90 (3) ◽  
pp. 166-169 ◽  
Author(s):  
M. H. G. M. Koppelman ◽  
M. S. Sjerps ◽  
M. Waal ◽  
H. W. Reesink ◽  
H. T. M. Cuypers
Keyword(s):  
West Nile Virus ◽  
Virus Infection ◽  
Blood Donors ◽  
West Nile Virus Infection ◽  
West Nile

The seroepidemiology and risk factors of West Nile virus infection in blood donors of Fars province, southwest of Iran

2021 ◽  
Author(s):  
Jamal Sarvari ◽  
Seyed Y Hosseini ◽  
Faezeh Mosayebi ◽  
Masoud T Ardekani ◽  
Negar Joharinia ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Blood Donors ◽  
Blood Donation ◽  
West Nile Virus Infection ◽  
Fars Province ◽  
West Nile ◽  
Transfusion Center ◽  
Blood Transfusion Center ◽  
Southwest Of Iran ◽  
Southwest Iran

Aim: To evaluate the frequency of West Nile virus (WNV) in blood donors of the blood transfusion center of Fars province, Iran. Materials & methods: A total of 337 participants referred for blood donation to Fars blood centers were included. The presence of anti-WNV antibodies was analyzed using the WNV IgG ELISA kit. Results: Out of all participants, 76 (22.6%) were positive for anti-WNV IgG antibodies. Our results also showed that the frequency of WNV was associated with the age, educational level, job and city of residency of participants (p < 0.05). Conclusion: The results indicated the high frequency of WNV seropositivity among blood donors in southwest Iran. Accordingly, there is an urgent need to establish an integrated surveillance system for monitoring WNV infection in Iran.

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