FISHing Out the Hidden Enemy: Advances in Detecting and Measuring Latent HIV-Infected Cells

The indomitable aspect of HIV-1 infection is not that HIV-1 proviral DNA is integrated into host DNA but that it can also turn itself off, remaining invisible to drug or immune surveillance. Thus, the goals of eradication include ways to precisely excise HIV-1 DNA or wake up the silent HIV-1 provirus and eliminate the infected cells thus identified. Methods to identify and fish out the latently infected cells or to delineate their characteristics are being rapidly developed. In 2016, Baxter et al. (A. E. Baxter, J. Niessl, R. Fromentin, J. Richard, F. Porichis, R. Charlebois, M. Massanella, N. Brassard, N. Alsahafi, G. G. Delgado, J. P. Routy, B. D. Walker, A. Finzi, N. Chomont, and D. E. Kaufmann, Cell Host Microbe 20: 368 -380, 2016, https://doi. org/ 10.1016/j. chom. 2016.07.015) and Martrus et al. (G. Martrus, A. Niehrs, R. Cornelis, A. Rechtien, W. Garcia-Beltran, M. Lutgehetmann, C. Hoffmann, and M. Altfeld, J Virol 90: 9018 -9028, 2016, https://doi. org/10.1128/JVI. 01448-16) reported using the fluorescence in situ hybridization-flow cytometry technique to identify and quantify cells expressing HIV-1 RNA and Gag protein, as well as bearing unique cell surface markers. In a recent article in mBio, Grau-Exposito et al. (J. Grau-Exposito, C. Serra-Peinado, L. Miguel, J. Navarro, A. Curran, J. Burgos, I. Ocana, E. Ribera, A. Torrella, B. Planas, R. Badia, J. Castellvi, V. Falco, M. Crespo, and M. J. Buzon, mBio 8: e00876-17, 2017, https://doi. org/10.1128/mBio. 00876-17) reported a similar method that they claim to be more sensitive. With these methods, researchers are one step closer to measuring latent reservoirs and eliminating critical barriers to HIV eradication.