Capsid lattice destabilization leads to premature loss of the viral genome and integrase enzyme during HIV-1 infection

March 26, 2020

Eschbach, J., Elliott, J., Li, W., et al.

BioRxiv 2020 doi: 10.1101/2020.03.26.009902

Abstract

The human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein forms a conical lattice around the viral ribonucleoprotein complex (vRNP) consisting of a dimeric viral genome and associated proteins, together constituting the viral core. Upon entry into target cells, the viral core undergoes a process termed uncoating, during which CA molecules are shed from the lattice. Although the timing and degree of uncoating are important for reverse transcription and integration, the molecular basis of this phenomenon remains unclear. Using complementary approaches, we assessed the impact of core destabilization on the intrinsic stability of the CA lattice in vitro and fates of viral core components in infected cells. We found that substitutions in CA can impact the intrinsic stability of the CA lattice in vitro in the absence of vRNPs, which mirrored findings from assessment of CA stability in virions. Altering CA stability tended to increase the propensity to form morphologically aberrant particles, in which the vRNPs were mislocalized between the CA lattice and the viral lipid envelope. Importantly, destabilization of the CA lattice led to premature dissociation of CA from vRNPs in target cells, which was accompanied by proteasomal-independent losses of the viral genome and integrase enzyme. Overall, our studies show that the CA lattice protects the vRNP from untimely degradation in target cells and provide the mechanistic basis of how CA stability influences reverse transcription.

View Publication

Topics: Tycho, Virology, Publications

Previous Article
The NanoTemper Story – Chapter 4: The Tycho
The NanoTemper Story – Chapter 4: The Tycho

What would you do if you created a brilliant new invention, but no one knew or understood why they would us...

Up next
Let's catalyze - biophysical insights into enzymes
Let's catalyze - biophysical insights into enzymes

Enzymes are nature's engine for many processes. Diving into the stability and function of enzymes will give...

Ready to understand your protein’s quality?

See what tools you can use

Learn more