Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Association between immunological events and changes in viral DNA and RNA burden in lymphoid organs of SIV-infected macaques and disease progression.
Symp Nonhum Primate Models AIDS. 1993 Sep 19-22;11:abstract no. 22. Unique Identifier : AIDSLINE PRIM11/94191615 Rosenberg YJ; Lewis MG; Leon EC; Eddy GA; Greenhouse J; Henry M. Jackson Foundation Research Laboratory, Rockville, MD.
Abstract:
Decline in the CD4+ T cells and HIV viral burden in the blood have been used as closely related correlates of disease progression. However since lymphocytes in the blood constitute only 1-2% of the total lymphocyte pool, it is important to understand how viral load in various organs in the lymphoid compartment are associated with their immunological degeneration and disease state. To achieve this, total (pol) viral DNA and unintegrated 2-LTR circular DNA levels as well as viral RNA expression were assessed in blood, spleen, lymph nodes (LN) and thymus from SIV-infected monkeys using PCR. Monkeys chronically infected with the SIV-251, SIV-E11S, and SIV-PBj-14 isolates were compared to determine how biologically different isolates alter the clinical course of disease. The results indicate that immunological collapse of LN occurs over a wide range of total viral DNA levels and does not always correlate with high rates of viral replication. A comparison of DNA levels following infection with different isolates indicates that SIV-251 infection results in > 10-fold higher levels of viral DNA than E11S or PBj-14 and may account for the more rapid disease progression. These DNA levels however do not predict progression to AIDS and do not directly correlate with the CD4% decline in nodes. Overall, the best correlate of LN collapse, both architectural and CD4/CD8 ratio decline, seen with advanced disease and/or death, is the significant increase in unintegrated viral DNA levels. This elevation appears to reflect a transition in viral synthesis from a primarily T-cell source to a predominantly macrophage source. To date, no close association between total viral DNA, unintegrated viral DNA and viral replication is apparent in the lymphoid organs studied.
Keywords: Animal CD4-CD8 Ratio DNA, Viral/*ANALYSIS/BIOSYNTHESIS Human HIV/PHYSIOLOGY Lymphoid Tissue/*MICROBIOLOGY Macaca Polymerase Chain Reaction/*METHODS RNA, Viral/*ANALYSIS/BIOSYNTHESIS Simian Acquired Immunodeficiency Syndrome/*IMMUNOLOGY/ MICROBIOLOGY/*PHYSIOPATHOLOGY SIV/GENETICS/ISOLATION & PURIF/*PHYSIOLOGY T-Lymphocyte Subsets/IMMUNOLOGY T-Lymphocytes/IMMUNOLOGY Virus Integration *Virus Replication ABSTRACT 940730
M9470903
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