Disseminated cytomegalovirus(CMV) infection is a frequent occurrence in AIDS in humans and in SIV-infected rhesus macaques. Reactivation of latent CMV infection is believed to occur as a result of HIV/SIV-induced immunosupression. Since CTL play a major role in control of viral infections, we set out to characterize CMV-specific CTL responses in SIV-infected and uninfected rhesus macaques. Experimental conditions for detection of CMV-specific CTL were initially established in CMV-seropositive, SIV-seronegative rhesus macaques. Autologous fibroblasts infected with a clinical rhesus CMV isolate were used to stimulate freshly isolated peripheral blood mononuclear cells (PBMC). Following in vitro stimulation for two weeks, specific CTL activity against CMV-infected autologous fibroblasts could be detected reproducibly in 4 of 4 CMV-seropositive adult breeder macaques. No CTL activity was detected when PBMC from these animals were stimulated in vitro with uninfected fibroblasts. Similarly, no CMV-specific CTL activity was detected using stimulated PBMC from a CMV-seronegative animal. CMV-specific CTL activity was also detected in two CMV seropositive macaques infected with a live attenuated SIV deficient in nef, LTR and vpr (SIV 3) and in two of 3 macaques chronically infected with a pathogenic SIV strain. The CMV-specific CTL response is MHC class I restricted, as shown by the ability of Brefeldin A, a selective blocker of the class I antigen presentation pathway, to abrogate lysis and by the partial to absent killing of allogeneic targets. In those cases where killing of allogeneic targets was observed, isoelectric focusing of immunoprecipitates of MHC class I molecules showed similar bands, suggesting shared MHC class I alleles. These studies will allow us to prospectively analyze CMV-specific cellular immune responses in SIV-infected animals and examine the host factors that correlate with reactivation of CMV.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000168-35
Application #
3719018
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
35
Fiscal Year
1996
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Shang, L; Smith, A J; Reilly, C S et al. (2018) Vaccine-modified NF-kB and GR signaling in cervicovaginal epithelium correlates with protection. Mucosal Immunol 11:512-522
Sonntag, Kai-Christian; Woo, Tsung-Ung W (2018) Laser microdissection and gene expression profiling in the human postmortem brain. Handb Clin Neurol 150:263-272
Almodovar, Sharilyn; Swanson, Jessica; Giavedoni, Luis D et al. (2018) Lung Vascular Remodeling, Cardiac Hypertrophy, and Inflammatory Cytokines in SHIVnef-Infected Macaques. Viral Immunol 31:206-222
Duke, Angela N; Meng, Zhiqiang; Platt, Donna M et al. (2018) Evidence That Sedative Effects of Benzodiazepines Involve Unexpected GABAA Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys. J Pharmacol Exp Ther 366:145-157
Kamberov, Yana G; Guhan, Samantha M; DeMarchis, Alessandra et al. (2018) Comparative evidence for the independent evolution of hair and sweat gland traits in primates. J Hum Evol 125:99-105
Seth, Nitin; Simmons, Heather A; Masood, Farah et al. (2018) Model of Traumatic Spinal Cord Injury for Evaluating Pharmacologic Treatments in Cynomolgus Macaques (Macaca fasicularis). Comp Med 68:63-73
Mauney, Sarah A; Woo, Tsung-Ung W; Sonntag, Kai C (2018) Cell Type-Specific Laser Capture Microdissection for Gene Expression Profiling in the Human Brain. Methods Mol Biol 1723:203-221
Termini, James M; Church, Elizabeth S; Silver, Zachary A et al. (2017) Human Immunodeficiency Virus and Simian Immunodeficiency Virus Maintain High Levels of Infectivity in the Complete Absence of Mucin-Type O-Glycosylation. J Virol 91:
Ma, Qi; Ruan, Hongyu; Peng, Lisheng et al. (2017) Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity. Proc Natl Acad Sci U S A 114:E8760-E8769
Shang, L; Duan, L; Perkey, K E et al. (2017) Epithelium-innate immune cell axis in mucosal responses to SIV. Mucosal Immunol 10:508-519

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