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Review
. 2020 Sep 9;12(9):1005.
doi: 10.3390/v12091005.

Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis

Jennifer L Elliott  1 , Sebla B Kutluay  1
Affiliations
Review

Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis

Jennifer L Elliott et al. Viruses. .

Abstract

The HIV-1 integrase enzyme (IN) plays a critical role in the viral life cycle by integrating the reverse-transcribed viral DNA into the host chromosome. This function of IN has been well studied, and the knowledge gained has informed the design of small molecule inhibitors that now form key components of antiretroviral therapy regimens. Recent discoveries unveiled that IN has an under-studied yet equally vital second function in human immunodeficiency virus type 1 (HIV-1) replication. This involves IN binding to the viral RNA genome in virions, which is necessary for proper virion maturation and morphogenesis. Inhibition of IN binding to the viral RNA genome results in mislocalization of the viral genome inside the virus particle, and its premature exposure and degradation in target cells. The roles of IN in integration and virion morphogenesis share a number of common elements, including interaction with viral nucleic acids and assembly of higher-order IN multimers. Herein we describe these two functions of IN within the context of the HIV-1 life cycle, how IN binding to the viral genome is coordinated by the major structural protein, Gag, and discuss the value of targeting the second role of IN in virion morphogenesis.

Keywords: HIV-1; integrase; integrase–RNA interactions; maturation; protein–RNA interactions.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Overview of the human immunodeficiency virus type 1 (HIV-1) life cycle highlighting the key role of HIV-1 integrase enzyme (IN) at early and late stages of replication.
Figure 2
Figure 2
Virion maturation and morphogenesis. (A) The Gag and Gag-Pol polyproteins assemble with vRNA at the plasma membrane, bud from the surface of the cell as immature virions, and then undergo a maturation process. (B) During maturation PR cleaves Gag and Gag-Pol into independent structural and replicative proteins.
Figure 3
Figure 3
Inhibition of IN–RNA interactions result in the formation of eccentric virions. Immature viral particles consist of many molecules of Gag and Gag–Pol concentrically arranged along the inner leaflet of the viral membrane and bound to viral RNA (vRNA) at the NC domain. In mature viral particles, the vRNA is bound by NC and condensed with RT and IN to form the vRNP, which is enclosed in the conical capsid lattice made up of CA monomers. In eccentric viral particles, as observed upon inhibition of IN binding to the viral genome, the vRNP is mislocalized outside of the capsid lattice.
See this image and copyright information in PMC

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