Protease inhibitors effectively block cell-to-cell spread of HIV-1 between T cells

Retrovirology

Clare Jolly¹  Deenan Pillay²  Marlen Aasa-Chapman¹  Boghuma Kabisen Titanji¹ 

[1] Division of Infection and Immunity, University College London, Cruciform Building, Gower St, London WC1E 6BT, United Kingdom;Africa Centre for Health and Population Sciences, University of KwaZulu Natal, KwaZulu-Natal, South Africa

关键词: ART;    Protease inhibitor;    Cell-cell spread;    Virological synapse;    HIV-1;   

Others  :  805467
DOI  :  10.1186/1742-4690-10-161

 received in 2013-10-11, accepted in 2013-12-11,  发布年份 2013

【 摘 要 】

Background

The Human Immunodeficiency Virus type-1 (HIV-1) spreads by cell-free diffusion and by direct cell-to-cell transfer, the latter being a significantly more efficient mode of transmission. Recently it has been suggested that cell-to-cell spread may permit ongoing virus replication in the presence of antiretroviral therapy (ART) based on studies performed using Reverse Transcriptase Inhibitors (RTIs). Protease Inhibitors (PIs) constitute an important component of ART; however whether this class of inhibitors can suppress cell-to-cell transfer of HIV-1 is unexplored. Here we have evaluated the inhibitory effect of PIs during cell-to-cell spread of HIV-1 between T lymphocytes.

Results

Using quantitative assays in cell line and primary cell systems that directly measure the early steps of HIV-1 infection we find that the PIs Lopinavir and Darunavir are equally potent against both cell-free and cell-to-cell spread of HIV-1. We further show that a protease resistant mutant maintains its resistant phenotype during cell-to-cell spread and is transmitted more efficiently than wild-type virus in the presence of drug. By contrast we find that T cell-T cell spread of HIV-1 is 4–20 fold more resistant to inhibition by the RTIs Nevirapine, Zidovudine and Tenofovir. Notably, varying the ratio of infected and uninfected cells in co-culture impacted on the degree of inhibition, indicating that the relative efficacy of ART is dependent on the multiplicity of infection.

Conclusions

We conclude that if the variable effects of antiviral drugs on cell-to-cell virus dissemination of HIV-1 do indeed impact on viral replication and maintenance of viral reservoirs this is likely to be influenced by the antiviral drug class, since PIs appear particularly effective against both modes of HIV-1 spread.

【 授权许可】

   
2013 Titanji et al.; licensee BioMed Central Ltd.

【 图 表 】

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