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Integrase-RNA interactions underscore the critical role of integrase in HIV-1 virion morphogenesis.

ABSTRACT: A large number of human immunodeficiency virus 1 (HIV-1) integrase (IN) alterations, referred to as class II substitutions, exhibit pleiotropic effects during virus replication. However, the underlying mechanism for the class II phenotype is not known. Here we demonstrate that all tested class II IN substitutions compromised IN-RNA binding in virions by one of the three distinct mechanisms: (i) markedly reducing IN levels thus precluding the formation of IN complexes with viral RNA; (ii) adversely affecting functional IN multimerization and consequently impairing IN binding to viral RNA; and (iii) directly compromising IN-RNA interactions without substantially affecting IN levels or functional IN multimerization. Inhibition of IN-RNA interactions resulted in the mislocalization of viral ribonucleoprotein complexes outside the capsid lattice, which led to premature degradation of the viral genome and IN in target cells. Collectively, our studies uncover causal mechanisms for the class II phenotype and highlight an essential role of IN-RNA interactions for accurate virion maturation.

SUBMITTER: Elliott JL

PROVIDER: S-EPMC7671690 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Integrase-RNA interactions underscore the critical role of integrase in HIV-1 virion morphogenesis.

Elliott Jennifer L JL Eschbach Jenna E JE Koneru Pratibha C PC Li Wen W Puray-Chavez Maritza M Townsend Dana D Lawson Dana Q DQ Engelman Alan N AN Kvaratskhelia Mamuka M Kutluay Sebla B SB

eLife 20200922

A large number of human immunodeficiency virus 1 (HIV-1) integrase (IN) alterations, referred to as class II substitutions, exhibit pleiotropic effects during virus replication. However, the underlying mechanism for the class II phenotype is not known. Here we demonstrate that all tested class II IN substitutions compromised IN-RNA binding in virions by one of the three distinct mechanisms: (i) markedly reducing IN levels thus precluding the formation of IN complexes with viral RNA; (ii) adverse ...[more]

PMID: 32960169

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Integrase-RNA interactions underscore the critical role of integrase in HIV-1 virion morphogenesis.

Publications

Integrase-RNA interactions underscore the critical role of integrase in HIV-1 virion morphogenesis.

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