Infectious SIV resides in adipose tissue and induces metabolic defects in chronically infected rhesus macaques.
BACKGROUND
HIV reservoirs pose major challenges to viral eradication. The main cellular reservoirs include CD4 T cells and macrophages, whereas anatomic reservoirs are thought to be primarily lymphoid tissues. Adipose tissue represents a potentially important non-lymphoid location for HIV replication and persistence because the stromal-vascular-fraction (AT-SVF) contains activated innate and adaptive immune cells that increase in number during infections, obesity, and chronic inflammation.


RESULTS
Adipose tissue from two groups of SHIV-SF162p3-infected (~4 weeks acute infection) or SIVmac251-infected (~38 weeks chronic infection) rhesus macaques (N = 8 for each group) were studied for immune cell content, viral infectiousness, and metabolic health. The AT-SVF cells from SHIV-infected monkeys contained abundant memory CD4 and CD8 T cells, with fewer NKT cells and macrophages, and no B cells. Proviral DNA (Gag and Env) was readily detectable by nested PCR in AT-SVF cells from multiple adipose depots (subcutaneous and visceral) of acutely infected monkeys, but mostly from visceral fat. More importantly, viral outgrowth assays using input CD4 T cells derived from AT-SVF cells or peripheral blood of chronically infected monkeys resulted in robust replication of infectious virus from both AT-SVF and peripheral blood CD4 T cells. Chronically infected monkeys also experienced adipocyte dysfunction (suppression of major adipogenic genes) and systemic dyslipidemia (decreased serum total cholesterol and free fatty acids, and increased triglycerides), similar to metabolic abnormalities of HIV patients.


CONCLUSIONS
Adipose tissues of SIV-infected rhesus macaques become major compartments for infected immune cells, which in turn induce defects in adipose tissue metabolism.
Division of Infectious Diseases, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.|Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Jacob
J
Couturier
Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Diabetes Research Center, Baylor College of Medicine, Houston, TX, USA.
Neeti
N
Agarwal
Department of Veterinary Sciences, The University of Texas MD Anderson Cancer Center, Bastrop, TX, USA.
Pramod N
PN
Nehete
Department of Veterinary Sciences, The University of Texas MD Anderson Cancer Center, Bastrop, TX, USA.
Wallace B
WB
Baze
Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.
Michael A
MA
Barry
Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.|Department of Veterinary Sciences, The University of Texas MD Anderson Cancer Center, Bastrop, TX, USA.|Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
K
K
Jagannadha Sastry
Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Diabetes Research Center, Baylor College of Medicine, Houston, TX, USA.|Endocrine Service, Ben Taub General Hospital, Houston, TX, USA.
Ashok
A
Balasubramanyam
Division of Infectious Diseases, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA. Dorothy.E.Lewis@uth.tmc.edu.|Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA. Dorothy.E.Lewis@uth.tmc.edu.
Dorothy E
DE
Lewis
D000273:Adipose Tissue / Q000821:virology*; D000818:Animals; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008253:Macaca mulatta; D008297:Male; D016133:Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification* / Q000502:physiology*
D004279:DNA, Viral
Adipose tissue; CD4 T cells; HIV latency; HIV reservoirs; Rhesus macaques; SIV reservoirs