Universität zu Köln

Lu, Ching-Lan, Pai, Joy A., Nogueira, Lilian, Mendoza, Pilar, Gruell, Henning, Oliveira, Thiago Y., Barton, John, Lorenzi, Julio C. C., Cohen, Yehuda Z., Cohn, Lillian B., Klein, Florian, Caskey, Marina, Nussenzweig, Michel C. and Jankovic, Mila (2018). Relationship between intact HIV-1 proviruses in circulating CD4(+) T cells and rebound viruses emerging during treatment interruption. Proc. Natl. Acad. Sci. U. S. A., 115 (48). S. E11341 - 8. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

Combination antiretroviral therapy controls but does not cure HIV-1 infection because a small fraction of cells harbor latent viruses that can produce rebound viremia when therapy is interrupted. The circulating latent virus reservoir has been documented by a variety of methods, most prominently by viral outgrowth assays (VOAs) in which CD4(+) T cells are activated to produce virus in vitro, or more recently by amplifying proviral near full-length (NFL) sequences from DNA. Analysis of samples obtained in clinical studies in which individuals underwent analytical treatment interruption (ATI), showed little if any overlap between circulating latent viruses obtained from outgrowth cultures and rebound viruses from plasma. To determine whether intact proviruses amplified from DNA are more closely related to rebound viruses than those obtained from VOAs, we assayed 12 individuals who underwent ATI after infusion of a combination of two monoclonal anti-HIV-1 antibodies. A total of 435 intact proviruses obtained by NFL sequencing were compared with 650 latent viruses from VOAs and 246 plasma rebound viruses. Although, intact NFL and outgrowth culture sequences showed similar levels of stability and diversity with 39% overlap, the size of the reservoir estimated from NFL sequencing was larger than and did not correlate with VOAs. Finally, intact proviruses documented by NFL sequencing showed no sequence overlap with rebound viruses; however, they appear to contribute to recombinant viruses found in plasma during rebound.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lu, Ching-Lan UNSPECIFIED UNSPECIFIED UNSPECIFIED Pai, Joy A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nogueira, Lilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Mendoza, Pilar UNSPECIFIED UNSPECIFIED UNSPECIFIED Gruell, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Oliveira, Thiago Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barton, John UNSPECIFIED UNSPECIFIED UNSPECIFIED Lorenzi, Julio C. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cohen, Yehuda Z. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cohn, Lillian B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Caskey, Marina UNSPECIFIED UNSPECIFIED UNSPECIFIED Nussenzweig, Michel C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jankovic, Mila UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-165356
DOI:	10.1073/pnas.1813512115
Journal or Publication Title:	Proc. Natl. Acad. Sci. U. S. A.
Volume:	115
Number:	48
Page Range:	S. E11341 - 8
Date:	2018
Publisher:	NATL ACAD SCIENCES
Place of Publication:	WASHINGTON
ISSN:	0027-8424
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LATENT RESERVOIR; IDENTIFICATION; RECOMBINATION; ANTIBODIES; SEQUENCE; THERAPY Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16535