The identification of distinct monocyte/macrophage populations that carry virus to the CNS and subsets within the CNS that are the target for infection by HIV/SIV is not defined In this study we have used immunohistochemistry and combined immunohistochemistry with in situ hybridization to define which populations of brain macrophages are infected at peak viremia and in SIVE Perivascular brain macrophages and the resident brain macrophage, microglia, are both CDllb and CD68 positive The perivascular macrophages, but not microglia, are also positive for CD14, CD45, and CD86 Multi-nucleated giant cells (MNGC), when present, are CD11b and CD68 positive like parenchymal microglia and perivascular macrophages The MNGC also are CD14 and CD45 positive, but express variable to non-detectable levels of CD4 Using combined immunohistochemistry and in situ hybridization and/or double label immunohistochemistry for myeloid cell markers followed by gp120, we demonstrat e th at the majority of gp120 or viral RNA positive cells are CD14 positive perivascular macrophages These perivascular cells are the major cell infected within the CNS during peak viremia (2 weeks post infection) and in animals with SIVE Less than 1% of the infected cells are resident microglia based upon immunohistochemistry These data underscore the importance of the perivascular macrophage as the major target of SIV in the CNS

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000168-40
Application #
6453757
Study Section
Project Start
2001-05-01
Project End
2002-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
40
Fiscal Year
2001
Total Cost
$111,112
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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