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Novel assays to investigate the mechanisms of latent infection with HIV-2
- Lu, Michael D;
- Telwatte, Sushama;
- Kumar, Nitasha;
- Ferreira, Fernanda;
- Martin, Holly Anne;
- Kadiyala, Gayatri Nikhila;
- Wedrychowski, Adam;
- Moron-Lopez, Sara;
- Chen, Tsui-Hua;
- Goecker, Erin A;
- Coombs, Robert W;
- Lu, Chuanyi M;
- Wong, Joseph K;
- Tsibris, Athe;
- Yukl, Steven A
- Editor(s): Kashanchi, Fatah
- et al.
Published Web Location
https://doi.org/10.1371/journal.pone.0267402Abstract
Although there have been great advancements in the field of HIV treatment and prevention, there is no cure. There are two types of HIV: HIV-1 and HIV-2. In addition to genetic differences between the two types of HIV, HIV-2 infection causes a slower disease progression, and the rate of new HIV-2 infections has dramatically decreased since 2003. Like HIV-1, HIV-2 is capable of establishing latent infection in CD4+ T cells, thereby allowing the virus to evade viral cytopathic effects and detection by the immune system. The mechanisms underlying HIV latency are not fully understood, rendering this a significant barrier to development of a cure. Using RT-ddPCR, we previously demonstrated that latent infection with HIV-1 may be due to blocks to HIV transcriptional elongation, distal transcription/polyadenylation, and multiple splicing. In this study, we describe the development of seven highly-specific RT-ddPCR assays for HIV-2 that can be applied to the study of HIV-2 infections and latency. We designed and validated seven assays targeting different HIV-2 RNA regions along the genome that can be used to measure the degree of progression through different blocks to HIV-2 transcription and splicing. Given that HIV-2 is vastly understudied relative to HIV-1 and that it can be considered a model of a less virulent infection, application of these assays to studies of HIV-2 latency may inform new therapies for HIV-2, HIV-1, and other retroviruses.
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