This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hepatitis C virus infections in man become chronic in approximately 85% percent of individuals exposed. At present there are an estimated 2.7 million chronically infected people in the United States and an estimated 200 million worldwide. There is no vaccine and therapy for chronic HCV infections is limited a combination of interferon and ribavirin, but treatment is successful in less than half the patients. There currently exist poor cell culture systems for the virus which have not proved to be reproducible between labs and the only animal model for the virus is the chimpanzee. Recently we succeeded in producing infectious hepatitis C virus in cell culture (termed HCVcc). The goal of this chimpanzee experiment is to test the infectivity of these particles in vivo. For most HCV isolates, adaptive mutations are required for efficient RNA replication in cell culture. Although only a limited number of these adaptive changes have been tested in vivo, they appear to be deleterious for replication in chimpanzees and have only rarely been detected in sequences of natural HCV isolates. Testing this isolate or cell culture infectious chimeras in chimpanzees is potentially of great importance to the HCV field. Until this point, HCV produced in vivo (from chimpanzees or humans) is non-infectious or poorly infectious in cell culture. Conversely, HCV RNAs adapted to replicate in cell culture are compromised in their ability to replicate in vivo. Having an isolate that can replicate both in cell culture and in vivo would be a very powerful tool for characterizing HCV replication, entry and pathogenesis. This will enable us to compare the behavior of true HCV particles produced in the liver to HCVcc produced in cell culture. The will be particularly important for studies of virus entry and neutralization and also reduce the need for future chimpanzee experiments. 10^6 cell culture infectious units of two different cell culture adapted viruses will be inoculated i.v. into two different animals. (Total volume ~1-2mL). The inoculum will consist of concentrated cell culture supernatant. Animals will be bled weekly and monitored for HCV viremia. If no infection is indicated after 8 weeks the animals will be challenged with a known infectious isolate (HCVH77 monoclonal virus) to demonstrate infectivity.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR013986-08
Application #
7349872
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2006-05-01
Project End
2007-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
8
Fiscal Year
2006
Total Cost
$11,603
Indirect Cost
Name
Texas Biomedical Research Institute
Department
Type
DUNS #
007936834
City
San Antonio
State
TX
Country
United States
Zip Code
78245
Jensen, Jeffrey T; Hanna, Carol; Mishler, Emily et al. (2018) Effect of menstrual cycle phase and hormonal treatments on evaluation of tubal patency in baboons. J Med Primatol 47:40-45
Confer, Alexandra; Owston, Michael A; Kumar, Shyamesh et al. (2018) Multiple endocrine neoplasia-like syndrome in 24 baboons (Papio spp.). J Med Primatol 47:434-439
Mustonen, Allison; Gonzalez, Olga; Mendoza, Elda et al. (2018) Uremic encephalopathy in a rhesus macaque (Macaca mulatta): A case report and a brief review of the veterinary literature. J Med Primatol :
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Mangosing, Sara; Perminov, Ekaterina; Gonzalez, Olga et al. (2018) Uterine Tumors Resembling Ovarian Sex Cord Tumors in Four Baboons ( Papio spp.). Vet Pathol 55:753-758
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Shelton, Elaine L; Waleh, Nahid; Plosa, Erin J et al. (2018) Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data. Pediatr Res 84:458-465
Perminov, Ekaterina; Mangosing, Sara; Confer, Alexandra et al. (2018) A case report of ovotesticular disorder of sex development (OT-DSD) in a baboon (Papio spp.) and a brief review of the non-human primate literature. J Med Primatol 47:192-197
Kumar, Shyamesh; Laurence, Hannah; Owston, Michael A et al. (2017) Natural pathology of the captive chimpanzee (Pan troglodytes): A 35-year review. J Med Primatol 46:271-290

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