Work

HIV-1 proviruses which are integrated into cancer-related genes are inducible

Year: 2017

Type: article

Abstract: Background: Accurate measurement of the latent reservoir is essential for the evaluation of cure strategies.Widely used PCR strategies mainly detect defective proviruses and vastly overestimate reservoir size while the viral outgrowth assay and other assays that measure viral RNA, protein or virion production following a single round of T cell activation miss proviruses that are only induced after multiple rounds.Therefore we developed a novel approach to reservoir measurement that directly quantitates intact proviruses that are capable of causing viral rebound.Methods: A large database of full genome sequences was used to design a digital droplet PCR assay that directly and separately quantitates intact and defective proviruses.Results: This approach gives infected cells frequencies that correlate well with results of full genome sequencing.Application to interesting patient populations has provided new insights into reservoir dynamics.Conclusions: Direct measurement of all of the intact proviruses capable of causing viral rebound with a novel rapid and scalable assay may provide the best way to evaluate cure strategies targeting the latent reservoir.

Source: Journal of Virus Eradication

DOI: 10.1016/s2055-6640(20)30520-3