Viral DNA burden and decline in percentage of CD4-positive cells in the lymphoid compartment of SIV-infected macaques.
The decline in CD4+ cells and increased viral DNA and RNA burden in the blood of human immunodeficiency virus (HIV)-infected individuals have been used as closely related correlates of disease progression. However, little is known about levels of total or unintegrated viral DNA in lymphoid tissue of HIV-infected patients and how they relate to CD4+ cell decline or disease progression. Exploiting the similarities between HIV- and simian immunodeficiency virus (SIV)-induced disease, we examined lymphoid organs and peripheral blood from SIV-infected macaques for total (pol) and unintegrated 2-LTR circular viral DNA by polymerase chain reaction (PCR). Two SIV isolates (SIVmac/251 and SIVmne/E11S) that differ markedly in their biological and clinical properties were studied. The results indicate that total viral DNA burdens vary considerably between isolates. There was no strong association between total viral DNA levels and CD4% in lymphoid tissues when isolates were compared and death was not associated with any particular level of viral pol DNA. In contrast, accumulation of unintegrated viral DNA was closely associated with decline in CD4/CD8 ratios in lymphoid organs and AIDS. The appearance of both pol and unintegrated viral DNA in thymus of infected macaques also emerged as one of the single best correlates or possible predictors of advanced disease yet studied. Their roles in pathogenesis are discussed.
Henry M. Jackson Foundation Laboratories, Rockville, Maryland 20850.
Y J
YJ
Rosenberg
M G
MG
Lewis
E C
EC
Leon
A
A
Cafaro
G A
GA
Eddy
J J
JJ
Greenhouse
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis* / Q000235:genetics; D015751:Genes, pol; D006678:HIV / Q000235:genetics; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D006801:Humans; D008251:Macaca; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D013950:Thymus Gland / Q000821:virology; D016662:Virus Integration
D000914:Antibodies, Viral; D017931:DNA Primers; D004279:DNA, Viral