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.
Highlights
Human immunodeficiency virus type 1 (HIV-1) is the causative agent of AIDS, and since its discovery in 1983 [1,2] has become one of the leading causes of the death worldwide due to infectious disease
The purpose of this review is to provide an overview of the multiple roles of integrase enzyme (IN) in the HIV-1 life cycle, with a focus on its function during virion maturation and morphogenesis
Treatment with allosteric IN inhibitors (ALLINIs) interferes with virion morphogenesis and leads to the generation of eccentric viral particles with viral ribonucleoprotein complex (vRNP) mislocalized outside the capsid lattice, strikingly similar to those generated by class II IN mutations [163,182,183,187,190]
Summary
Human immunodeficiency virus type 1 (HIV-1) is the causative agent of AIDS, and since its discovery in 1983 [1,2] has become one of the leading causes of the death worldwide due to infectious disease. The HIV-1 integrase enzyme (IN) plays a vital role in the viral life cycle by catalyzing the integration of viral DNA into the host chromosome. This function has been successfully targeted by a class of antiretrovirals known as integrase strand-transfer inhibitors (INSTIs) [3]. Loss of IN–RNA binding leads to mislocalization of the viral genome in virions and prevents viral replication in target cells [18]. This discovery opens up new avenues for therapeutic targeting of the second function of IN that is independent of its already. The value of targeting virion morphogenesis as a therapeutic strategy will be discussed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
