A recombinant virus assay using full-length envelope sequences to detect changes in HIV-1 co-receptor usage

Dittmar, Matthias T., Eichler, Stefanie, Reinberger, Stefanie, Henning, Lars, and Kräusslich, Hans-Georg (2001) A recombinant virus assay using full-length envelope sequences to detect changes in HIV-1 co-receptor usage. Virus Genes, 23 (3). pp. 281-290.

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The clinical management of HIV-1 infection has benefited enormously from molecular characterization of drug resistance as well as determination of the viral phenotype in vitro. HIV-1 infected individuals on HAART are currently monitored for the development of drug resistance variants allowing clinicians to redesign drug regimens. An understanding of the molecular basis of the evolution of drug resistance in vivo allows the improvement of the drugs as well as in vitro evaluation of new antiviral compounds alone or in combination with those currently approved. New findings suggest that viral envelopes could be a target to inhibit infection and replication. Therefore the generation of a recombinant virus assay (RVA) to allow the phenotypic determination of drug resistance against entry inhibitors (EI) is anticipated. We constructed an env-deleted clone of HIV-1 using the molecular clone NL-4.3. PCR amplified complete envelope genes (NL-4.3, BaL, primary envelope-genes) were ligated in vitro with a deletion clone (pNL-deltaK) and PM1-cells, supporting the replication of R5- and X4-tropic viruses, were transfected. Determination of co-receptor usage of the harvested recombinant virus-swarm revealed no difference compared to the molecular clones derived individually from three different patients. These results clearly show that an envelope-based RVA is practicable to monitor HIV-co-receptor usage at a given time point. Furthermore, this assay will allow to monitor resistance development against existing and future entry inhibitors and will aid to improve the management of HIV-therapy.

Item ID: 49865
Item Type: Article (Research - C1)
ISSN: 1572-994X
Keywords: recombinant virus assay, viral phenotype, resistance
Funders: Federal Ministry of Education and Research (BMBF), German Research Foundation (DFG)
Projects and Grants: DFG Di 777/2-1
Date Deposited: 15 Aug 2017 02:04
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111717 Primary Health Care @ 100%
SEO Codes: 92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920499 Public Health (excl. Specific Population Health) not elsewhere classified @ 100%
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