Effect of exogenous expression of IFN-γ on the new world alphavirus replication and infection

2019 ◽  
Vol 14 (9) ◽  
pp. 593-604
Author(s):  
Josh QH Wu ◽  
Nicole D Barabé ◽  
Damon Chau

Aim: IFN-γ plays an important role in control of the old world alphavirus infection. However, the role of IFN-γ in the infection by the new world alphaviruses is not well characterized. Materials & methods: Ad5-mIFN-γ, a recombinant, replication-deficient human adenovirus, was constructed to express mouse IFN-γ (mIFN-γ) and a mouse, lethal challenge model of the new world alphavirus western equine encephalitis virus (WEEV) was used. Results: A single-dose injection of Ad5-mIFN-γ produced a high level of mIFN-γ in mice. Cells inoculated with Ad5-mIFN-γ restricted the replication of WEEV. A single-dose injection of Ad5-mIFN-γ delayed the WEEV infection and extended the survival time in mice. Conclusion: IFN-γ restricts the WEEV infection.

2010 ◽  
Vol 84 (19) ◽  
pp. 9775-9782 ◽  
Author(s):  
Michael B. Sherman ◽  
Scott C. Weaver

ABSTRACT Western equine encephalitis virus (WEEV; Togaviridae, Alphavirus) is an enveloped RNA virus that is typically transmitted to vertebrate hosts by infected mosquitoes. WEEV is an important cause of viral encephalitis in humans and horses in the Americas, and infection results in a range of disease, from mild flu-like illnesses to encephalitis, coma, and death. In addition to spreading via mosquito vectors, human WEEV infections can potentially occur directly via aerosol transmission. Due to its aerosol infectivity and virulence, WEEV is thus classified as a biological safety level 3 (BSL-3) agent. Because of its highly infectious nature and containment requirements, it has not been possible to investigate WEEV's structure or assembly mechanism using standard structural biology techniques. Thus, to image WEEV and other BSL-3 agents, we have constructed a first-of-its-kind BSL-3 cryoelectron microscopy (cryoEM) containment facility. cryoEM images of WEEV were used to determine the first three-dimensional structure of this important human pathogen. The overall organization of WEEV is similar to those of other alphaviruses, consistent with the high sequence similarity among alphavirus structural proteins. Surprisingly, the nucleocapsid of WEEV, a New World virus, is more similar to the Old World alphavirus Sindbis virus than to other New World alphaviruses.


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