TY - JOUR
T1 - Going beyond Integration
T2 - The Emerging Role of HIV-1 Integrase in Virion Morphogenesis
AU - Elliott, Jennifer L.
AU - Kutluay, Sebla B.
N1 - Funding Information:
Funding: This study was supported by NIH grants U54AI150470 (the Center for HIV RNA Studies) and AI150497 to SBK and AI143389-F31 fellowship to JE.
Publisher Copyright:
© 2020 by the authors.
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
KW - HIV-1
KW - Integrase
KW - Integrase–RNA interactions
KW - Maturation
KW - Protein–RNA interactions
UR - http://www.scopus.com/inward/record.url?scp=85090845490&partnerID=8YFLogxK
U2 - 10.3390/v12091005
DO - 10.3390/v12091005
M3 - Review article
C2 - 32916894
AN - SCOPUS:85090845490
SN - 1999-4915
VL - 12
JO - Viruses
JF - Viruses
IS - 9
M1 - 1005
ER -