title: Correlation between viral RNA levels but not immune responses in plasma and tissues of macaques with long-standing SIVmac251 infection.
abstract: Plasma virus in human immunodeficiency virus type 1/simian immunodeficiency virus (HIV-1/SIV) infection most likely results from the combination of viruses produced in different tissues. As immunological pressure may be higher in effector sites than secondary lymphoid tissues, we investigated quantitative and qualitative changes in viral RNA in blood and tissues of 10 Mamu-A*01-positive SIV-infected macaques in parallel with the frequency of CD8+ T cells recognizing the dominant Gag181-189 CM9 epitope. The plasma virus level in these macaques directly correlated with the viral RNA levels in lymph nodes, spleen, lungs, colon, and jejunum. In contrast, the frequency of the Gag181-189 CM9 tetramer did not correlate with SIV RNA levels in any compartment. We investigated the presence of viral immune escape in RNA from several tissues. The complete substitution of wild-type genotype with viral immune-escape variant within the Gag181-189 CM9 epitope was associated with low tetramer response in all tissues and blood of two macaques. In one macaque, the replacement of wild type with an immune-escape mutant was asynchronous. While the mutant virus was prevalent in blood and effector tissues (lungs, jejunum, and colon), secondary lymphoid organs such as spleen and lymph nodes still retained 80% and 40%, respectively, of the wild-type virus. These results may imply that there are differences in the immunological pressure exerted by cytotoxic T lymphocytes (CTLs) in tissue compartments of SIVmac251-infected macaques.
authors.affiliation: Animal Models and Retroviral Vaccines Section, National Cancer Institute, 41/D804, Bethesda, MD 20892, USA.
authors.forename: Marcin
authors.initials: M
authors.lastname: Moniuszko
authors.forename: Derek
authors.initials: D
authors.lastname: Bogdan
authors.forename: Ranajit
authors.initials: R
authors.lastname: Pal
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Liljana
authors.initials: L
authors.lastname: Stevceva
authors.forename: Janos
authors.initials: J
authors.lastname: Nacsa
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Tryniszewska
authors.forename: Yvette
authors.initials: Y
authors.lastname: Edghill-Smith
authors.forename: Steven M
authors.initials: SM
authors.lastname: Wolinsky
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D003430:Cross-Sectional Studies; D000939:Epitopes / Q000235:genetics; D007422:Intestines / Q000821:virology; D008168:Lung / Q000821:virology; D008198:Lymph Nodes / Q000821:virology; D008251:Macaca; D009154:Mutation; D012367:RNA, Viral / Q000032:analysis / Q000097:blood*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D013154:Spleen / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D012367:RNA, Viral