Our project focuses on medically important Category A, B, and C bunyaviruses that cause hemorrhagic fever, cardiopulmonary manifestations, and encephalitis in humans. Most bunyaviruses are arboviruses with a life cycle involving replication in warm-blooded vertebrate species and arthropod vectors in nature. Species central to this proposal include Crimean Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus (RVFV), Sin Nombre virus (SNV), and LaCrosse virus (LACV). These viruses epitomize emerging zoonotic viruses that threaten human populations due to changing geographic and environmental interactions among human and natural reservoirs harboring these viruses. Our project is based on preliminary data indicating that bunyavirus replication physically engages with the cytoplasmic mRNA degradation and related RNA control pathways during replication. We used microarray data to define a set of cellular genes from these control pathways that are similarly up- or down-regulated following infection CCHFV, RVFV, and SNV. The project is organized around two specific aims.
Aim 1 is to identify cellular target gene(s) from our restricted starting set of candidate host factors that are required for bunyavirus replication. Such cellular factors would be attractive candidates of high potential for therapeutic intervention.
Aim 2 with test the hypothesis that those genes required for bunyavirus replication are necessary for efficient viral transcription or genome replication.

Public Health Relevance

The bunyaviruses include a set of problematic, emerging, zoonotic viruses that are harbored in a variety of vertebrate host reservoirs in nature, and transmitted to humans usually through arthropod vectors. Members of the family cause diseases ranging from hemorrhagic fever to more localized cardiopulmonary syndrome. Our project focuses on an important set of Category A, B, and C pathogenic bunyaviruses, and seeks to identify cellular components RNA control pathways required for virus replication.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AI057156-10
Application #
8566458
Study Section
Special Emphasis Panel (ZAI1-DDS-M)
Project Start
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2015-02-28
Support Year
10
Fiscal Year
2013
Total Cost
$252,053
Indirect Cost
$37,252
Name
University of Texas Medical Br Galveston
Department
Type
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
Paterson, Andrew S; Raja, Balakrishnan; Garvey, Gavin et al. (2014) Persistent luminescence strontium aluminate nanoparticles as reporters in lateral flow assays. Anal Chem 86:9481-8
Santiago, Felix W; Covaleda, Lina M; Sanchez-Aparicio, Maria T et al. (2014) Hijacking of RIG-I signaling proteins into virus-induced cytoplasmic structures correlates with the inhibition of type I interferon responses. J Virol 88:4572-85
Pflughoeft, Kathryn J; Swick, Michelle C; Engler, David A et al. (2014) Modulation of the Bacillus anthracis secretome by the immune inhibitor A1 protease. J Bacteriol 196:424-35
Lavinder, Jason J; Wine, Yariv; Giesecke, Claudia et al. (2014) Identification and characterization of the constituent human serum antibodies elicited by vaccination. Proc Natl Acad Sci U S A 111:2259-64
Valbuena, Gustavo; Halliday, Hailey; Borisevich, Viktoriya et al. (2014) A human lung xenograft mouse model of Nipah virus infection. PLoS Pathog 10:e1004063
Nieves, Wildaliz; Petersen, Hailey; Judy, Barbara M et al. (2014) A Burkholderia pseudomallei outer membrane vesicle vaccine provides protection against lethal sepsis. Clin Vaccine Immunol 21:747-54
Gardner, Christina L; Hritz, Jozef; Sun, Chengqun et al. (2014) Deliberate attenuation of chikungunya virus by adaptation to heparan sulfate-dependent infectivity: a model for rational arboviral vaccine design. PLoS Negl Trop Dis 8:e2719
Litvinov, Julia; Hagström, Anna E V; Lopez, Yubitza et al. (2014) Ultrasensitive immuno-detection using viral nanoparticles with modular assembly using genetically-directed biotinylation. Biotechnol Lett 36:1863-8
Caro-Gomez, Erika; Gazi, Michal; Goez, Yenny et al. (2014) Discovery of novel cross-protective Rickettsia prowazekii T-cell antigens using a combined reverse vaccinology and in vivo screening approach. Vaccine 32:4968-76
Georgiou, George; Ippolito, Gregory C; Beausang, John et al. (2014) The promise and challenge of high-throughput sequencing of the antibody repertoire. Nat Biotechnol 32:158-68

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