Browsing by Subject "Rift Valley fever virus"
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Item Predicting the Introduction and Transmission of Rift Valley Fever Virus in the United States(2014-12-09) Golnar, Andrew JohnRift Valley fever virus (RVFV) is a mosquito-borne virus in the family Bunyaviridae that has spread throughout continental Africa to Madagascar and the Arabian Peninsula. The establishment of RVFV in North America would have serious consequences for human and animal health in addition to a significant economic impact on the livestock industry. Specific objectives of this thesis are to identify high-risk regions involved in RVFV importation to the U.S., evaluate pathways of introduction, and theoretically quantify the relative importance of local vectors and vertebrate hosts to RVFV transmission should the virus reach the U.S. To estimate the relative risk of RVFV introduction to the U.S., the number of infectious mosquitoes arriving in the U.S. was quantified for five pathways: infected mosquitoes arriving by airplane, infected mosquitoes arriving by boat, infected mosquitoes arriving through tire trade, infected humans arriving by flight, and the trade of infected mammals. Results suggest that mosquito transport by airplane, mosquito transport by ship, and human travel are important pathways for RVFV introduction to the U.S. New York, Houston, Washington D.C., and Atlanta are high-risk regions for RVFV introduction in the U.S. Further, Saudi Arabia, South Africa, Nigeria, Egypt, Senegal, Ethiopia, Yemen and Angola are identified as regions at-risk for importing RVFV to the U.S. Published and unpublished data on RVFV vector competence, vertebrate host competence, and mosquito feeding patterns from the United States were combined to quantitatively implicate mosquito vectors and vertebrate hosts that may be important to RVFV transmission in the United States. A viremia-vector competence relationship based on published mosquito transmission studies was used to calculate a vertebrate host competence index which was then combined with mosquito blood feeding patterns to approximate the relative contribution of a mosquito or vertebrate host to RVFV transmission. Results implicate several Aedes spp. mosquitoes and vertebrates in the order Artiodactyla as important hosts for RVFV transmission in the U.S. Moreover, this study identifies critical gaps in knowledge necessary to comprehensively evaluate the different contributions of mosquitoes and vertebrates to potential RVFV transmission in the U.S.Item Reverse genetics system and fucntion of NSM protein of Rift Valley fever virus (family Bunyaviridae, genus phlebovirus)(2007-11-07) Sungyong Won; Shinji Makino; Thomas K. Hughes; Sankar Mitra; Robert E. JohnstonRift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) has a tripartite negative-strand genome, causes a mosquito-borne disease that is endemic in sub-Saharan African countries and results in large epidemics among humans and livestock. Furthermore, it has potential as a bioterrorist agent and poses a risk for introduction to other areas. In spite of its danger, neither veterinary nor human vaccines are available. I established a T7 RNA polymerase-based reverse genetics system to rescue infectious clones of RVFV MP-12 strain entirely from cDNA, the first for any phleboviruses. Using this system, RVFV carrying substitution mutations of the M gene preglycoprotein region (pre-Gn region), one lacking NSm protein expression, one lacking 78-kDa protein expression, and one lacking expression of both proteins, were rescued and compared in cell culture. All of the mutants and their parent virus produced plaques with similar sizes and morphologies in Vero E6 cells and had similar growth kinetics in Vero, C6/36, and MRC5 cells, demonstrating that the NSm and 78-kDa proteins were not needed for the virus to replicate efficiently in cell culture. A competition-propagation assay revealed that the parental virus was slightly more fit than the mutant virus lacking expression of both proteins. To determine the biological functions of the NSm and 78-kDa proteins, I generated the mutant virus, arMP-12-del21/384, carrying a large deletion in the pre-Gn region of the M segment. Neither NSm nor the 78-kDa proteins were synthesized in arMP-12-del21/384-infected cells. Although arMP-del21/384 and its parental arMP-12 showed similar virus growth kinetics, viral RNA, and proteins accumulation in infected cells, arMP-12-del21/384 infection induced extensive cell death and produced larger plaques than did the arMP-12 infection. arMP-12-del21/384 replication triggered apoptosis, including caspase-3 activation, cleavage of its downstream substrate, poly-ADP-ribose polymerase, and activation of initiator caspases, caspase-8 and -9, early in infection as compared with arMP-12 replication. NSm expression in arMP-12-del21/384-infected cells suppressed the severity of caspase-3 activation. Further, NSm protein expression inhibited staurosporine-induced activation of caspase-8 and -9, demonstrating that other viral proteins were dispensable for the NSm’s function in inhibiting apoptosis. RVFV NSm protein is the first identified Phleobovirus protein that has antiapoptotic function.