Language

English

Publication Date

7-16-2025

Journal

The Journal of Infectious Diseases

DOI

10.1093/infdis/jiaf373

PMID

40668935

PMCID

PMC12746608

PubMedCentral® Posted Date

12-30-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Background: Human immunodeficiency virus (HIV) establishes persistent infection by integrating its proviral DNA into the host genome. While most integrated proviruses are defective, a small portion of proviruses are intact that represent a major obstacle to achieving an HIV cure. We have designed an approach for selective elimination of host cells harboring replication-competent HIV (SECH), through inhibition of autophagy and anti-apoptotic molecules during viral reactivation. However, the effects of SECH on the dynamics of intact and defective HIV provirus remain unclear.

Methods: We isolated DNA from HIV-infected samples after SECH treatments. We analyzed HIV-1 proviruses in these samples by intact proviral DNA assay, near full-length PCR and DNA sequencing analyses.

Results: We show that SECH treatments reduce reservoirs harboring intact but not defective HIV proviruses by intact proviral DNA assays. Nested PCR and DNA sequencing analyses confirm that SECH treatments can delete full-length HIV-1 proviruses in humanized mice in vivo, and in patient samples ex vivo.

Conclusions: Our data suggest that the SECH method is capable of effectively targeting HIV reservoirs harboring intact HIV proviruses that can restart active viral replication.

Keywords

HIV, provirus, apoptosis, autophagy

Published Open-Access

yes

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