The development of an effective AIDS vaccine remains one of the highest priorities in HIV research. Studies of HIV pathogenesis, vaccine design and antiretroviral treatments require the use of an appropriate animal model. However, the currently used SIV/rhesus macaque (RM) model has serious limitations. The overall objective of this HIVRAD proposal is identify and characterize novel, moleculariy defined, physiologically relevant SIVsmm strains that reproducibly lead to productive infection in RMs and more faithfully recapitulate the genetic diversity and the clinical outcome of currently circulating HIV-1 strains. These new challenge strains will also be used to provide new mechanistic insight into mucosal HIV/SIV transmission. The Nonhuman Primate Core located at the University of Pittsburgh will be responsible for managing a large portion of the primate studies required for this Program Projects.
The Specific Aims i nclude: 1. To select, monitor and manage all non-human primates required by Projects 1 and 2. The goals are to provide these projects with the appropriate animals for the proposed studies, to ensure high quality animal housing and general husbandry, and to perform all aspects of the clinical management of the animals, including the care, treatment and long-term monitoring. 2. To coordinate the design and scheduling of non-human primate studies within the HIVRAD consortium. The goals are to coordinate the experimental design, arrange for efficient scheduling, collect, process, store and inventory all samples from RMs, and distribute the samples to the research groups. 3. To perform all necropsies required by Projects 1 and 2. The goals are to arrange for tissue collection, processing and storage, perform mononuclear cell separation from blood, non-lymphoid and lymphoid tissues and conduct all histopathological examinations. The purpose of the Animal Core Component is to provide high quality of animal care and housing, execution of study protocols, specimen collection and processing, performance of necropsies, and acquisition and management of animal clinical and pathological data necessary to meet the program research objectives. Dr. Pandrea and the Core team will closely interact with Project leaders and their laboratory staff to ensure timely completion of all NHP related research goals.
Results from these HIVRAD studies will shed new light on the molecular mechanisms underiying mucosal HIV/SIV transmission, identify new targets for vaccine-elicited immune responses, and generate a much needed set of new genetically-diverse SIVsmm/mac challenge strains for transmission, pathogenesis and AIDS vaccine research.
|Li, Hui; Wang, Shuyi; Kong, Rui et al. (2016) Envelope residue 375 substitutions in simian-human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques. Proc Natl Acad Sci U S A 113:E3413-22|
|Mason, Rosemarie D; Welles, Hugh C; Adams, Cameron et al. (2016) Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability. PLoS Pathog 12:e1005537|
|Raehtz, Kevin; Pandrea, Ivona; Apetrei, Cristian (2016) The well-tempered SIV infection: Pathogenesis of SIV infection in natural hosts in the wild, with emphasis on virus transmission and early events post-infection that may contribute to protection from disease progression. Infect Genet Evol :|
|Pandrea, Ivona; Xu, Cuiling; Stock, Jennifer L et al. (2016) Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques. PLoS Pathog 12:e1005384|
|Bailey, Adam L; Lauck, Michael; Sibley, Samuel D et al. (2015) Zoonotic Potential of Simian Arteriviruses. J Virol 90:630-5|
|Policicchio, Benjamin B; Pandrea, Ivona; Apetrei, Cristian (2015) Population Bottlenecks and Pathogen Extinction: "Make This Everyone's Mission to Mars, Including Yours". J Virol 89:8104-6|
|Ma, Dongzhu; Xu, Cuiling; Cillo, Anthony R et al. (2015) Simian Immunodeficiency Virus SIVsab Infection of Rhesus Macaques as a Model of Complete Immunological Suppression with Persistent Reservoirs of Replication-Competent Virus: Implications for Cure Research. J Virol 89:6155-60|
|Barbian, Hannah J; Decker, Julie M; Bibollet-Ruche, Frederic et al. (2015) Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas. MBio 6:|
|Langer, Simon M; Hopfensperger, Kristina; Iyer, Shilpa S et al. (2015) A Naturally Occurring rev1-vpu Fusion Gene Does Not Confer a Fitness Advantage to HIV-1. PLoS One 10:e0142118|
|Ma, Dongzhu; Jasinska, Anna J; Feyertag, Felix et al. (2014) Factors associated with siman immunodeficiency virus transmission in a natural African nonhuman primate host in the wild. J Virol 88:5687-705|
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