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Updated: Aug 6, 2025

Amplification of Near Full-length HIV-1 Proviruses for Next-Generation Sequencing
Published on: October 16, 2018
Nonsuppressible viremia during HIV-1 therapy meets molecular virology
Ann Emery1, Sarah B Joseph1,2,3, Ronald Swanstrom1,4
1Lineberger Comprehensive Cancer Center.
Abstract:
HIV-1 replication can be suppressed with antiretroviral therapy (ART), but individuals who stop taking ART soon become viremic again. Some people experience extended times of detectable viremia despite optimal adherence to ART. In this issue of the JCI, White, Wu, and coauthors elucidate a source of nonsuppressible viremia (NSV) in treatment-adherent patients - clonally expanded T cells harboring HIV-1 proviruses with small deletions or mutations in the 5'-leader, the UTR that includes the major splice donor site of viral RNA. These mutations altered viral RNA-splicing efficiency and RNA dimerization and packaging, yet still allowed production of detectable levels of noninfectious virus particles. These particles lacked the HIV-1 Env surface protein required for cell entry and failed to form the mature capsid cone required for infectivity. These studies improve our understanding of NSV and the regulation of viral functions in the 5'-leader with implications for rationalized care in individuals with NSV.
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