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1994-09-05
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Document 0836
DOCN M9480836
TI Polymerase chain reaction detection of HIV-1 2-LTR circular DNA may
predict CD4 decline.
DT 9410
AU Byrne BC; Parisi JM; Baxter JD; UMDNJ/RWJ Medical School, Camden 08103.
SO Abstr Gen Meet Am Soc Microbiol. 1994;94:555 (abstract no. C-368).
Unique Identifier : AIDSLINE ASM94/94313109
AB CD4(+)-T cell counts reflect a consequence of HIV infection but are not
markers of viral activity. We seek ways to monitor aspects of HIV
infection as potential tools in clinical trials of antiretroviral agents
or clinical management of infected patients. HIV RNA genomes are reverse
transcribed into double stranded linear DNA molecules following cellular
infection. The linear molecule may integrate into the host chromosome
initiating a new focus of infection or, linking the 5' and 3' LTR
regions, circularize. Proviral 2-LTR circles are apparent dead ends in
the retroviral life cycle, but provide unique targets for polymerase
chain reaction (PCR). Appropriately designed primers within the LTR will
fail to produce product from linear proviral DNA because (1) they are
directed outward from one another or (2) they span too large a sequence
(ca. 9KB) to form PCR product. Circles, by their topography, yield PCR
products and may be used generically for the low molecular weight
proviral DNA indicative of recent retroviral activity. We designed
nested primers within the LTR of HIV-1 to amplify closed circular DNA
and retrospectively selected 12 samples of peripheral blood mononuclear
cells from 12 patients having CD4 counts of approximately 500,
approximately 200 or approximately 20 cells/mm3 at the time of sampling.
These patients thereafter either exhibited stable or declining counts.
Quantitative PCR for HIV circles was most intense for two patients in
the approximately 500 CD4 class; these two patients also showed the most
profound rate of CD4 decline. Abundant closed circular DNA detected by
PCR may be a marker of retroviral activity that heralds imminent CD4
decline and might have implications for antiretroviral therapy.
DE Acquired Immunodeficiency Syndrome/CLASSIFICATION/*IMMUNOLOGY DNA,
Circular/*ANALYSIS DNA, Viral/*ANALYSIS Human *HIV Long Terminal
Repeat HIV-1/GENETICS/*ISOLATION & PURIF HIV-2/GENETICS/*ISOLATION &
PURIF Polymerase Chain Reaction/*METHODS Predictive Value of Tests T4
Lymphocytes/*IMMUNOLOGY/MICROBIOLOGY MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).