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Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
Antiretroviral agents effectively block HIV replication after cell-to-cell transfer
Marc Permanyer1, Ester Ballana, Alba Ruiz
1IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
Journal of Virology
|June 15, 2012
Summary
Cell-to-cell HIV transmission can evade antiretrovirals. However, quantitative analysis shows that HIV drugs effectively block viral DNA and replication in this transmission route, similar to cell-free infections.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Cell-to-cell transmission of Human Immunodeficiency Virus (HIV) is a proposed mechanism for viral escape from antiretroviral drugs.
- Understanding HIV persistence during antiretroviral therapy (ART) is crucial for effective treatment strategies.
Purpose of the Study:
- To evaluate HIV transmission dynamics between infected and uninfected cells (cell-associated infection).
- To assess the efficacy of antiretroviral agents in blocking cell-to-cell HIV transmission.
- To determine if common markers accurately reflect drug efficacy in cell-associated HIV transmission.
Main Methods:
- Coculture of HIV-1 infected cells with primary CD4(+) T cells or lymphoid cells.
- Treatment with reverse transcriptase inhibitors (zidovudine, tenofovir) and an attachment inhibitor (IgGb12).
- Quantitative measurement of viral DNA production and HIV-1 long terminal repeat (LTR)-driven green fluorescent protein (GFP) expression.
Main Results:
- HIV antigen transfer was resistant to reverse transcriptase inhibitors but blocked by an attachment inhibitor.
- Quantitative viral DNA production revealed that all tested antiretrovirals potently inhibited replication in cell-associated transmission.
- Replication-independent Tat-mediated LTR transactivation can confound GFP detection, potentially misestimating drug efficacy in cell-associated transmission.
Conclusions:
- Common markers of viral replication may not accurately measure infectivity or antiretroviral efficacy in cell-to-cell HIV transmission.
- Accurate quantification confirms that antiretrovirals effectively block proviral DNA and replication in cell-to-cell transmission.
- The efficacy of antiretrovirals in cell-to-cell HIV transmission mirrors their effectiveness in cell-free infections and in vivo.
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