Advertisement

 

 

Molecular mechanisms by which HERV-K Gag interferes with HIV-1 Gag assembly and particle infectivity.

Molecular mechanisms by which HERV-K Gag interferes with HIV-1 Gag assembly and particle infectivity.
Author Information (click to view)

Monde K, Terasawa H, Nakano Y, Soheilian F, Nagashima K, Maeda Y, Ono A,


Monde K, Terasawa H, Nakano Y, Soheilian F, Nagashima K, Maeda Y, Ono A, (click to view)

Monde K, Terasawa H, Nakano Y, Soheilian F, Nagashima K, Maeda Y, Ono A,

Advertisement

Retrovirology 2017 04 2614(1) 27 doi 10.1186/s12977-017-0351-8

Abstract
BACKGROUND
Human endogenous retroviruses (HERVs), the remnants of ancient retroviral infections, constitute approximately 8% of human genomic DNA. Since HERV-K Gag expression is induced by HIV-1 Tat in T cells, induced HERV-K proteins could affect HIV-1 replication. Indeed, previously we showed that HERV-K Gag and HIV-1 Gag coassemble and that this appears to correlate with the effect of HERV-K Gag expression on HIV-1 particle release and its infectivity. We further showed that coassembly requires both MA and NC domains, which presumably serve as scaffolding for Gag via their abilities to bind membrane and RNA, respectively. Notably, however, despite possessing these abilities, MLV Gag failed to coassemble with HIV-1 Gag and did not affect assembly and infectivity of HIV-1 particles. It is unclear how the specificity of coassembly is determined.

RESULTS
Here, we showed that coexpression of HERV-K Gag with HIV-1 Gag changed size and morphology of progeny HIV-1 particles and severely diminished infectivity of such progeny viruses. We further compared HERV-K-MLV chimeric constructs to identify molecular determinants for coassembly specificity and for inhibition of HIV-1 release efficiency and infectivity. We found that the CA N-terminal domain (NTD) of HERV-K Gag is important for the reduction of the HIV-1 release efficiency, whereas both CA-NTD and major homology region of HERV-K Gag contribute to colocalization with HIV-1 Gag. Interestingly, these regions of HERV-K Gag were not required for reduction of progeny HIV-1 infectivity.

CONCLUSIONS
Our results showed that HERV-K Gag CA is important for reduction of HIV-1 release and infectivity but the different regions within CA are involved in the effects on the HIV-1 release and infectivity. Altogether, these findings revealed that HERV-K Gag interferes the HIV-1 replication by two distinct molecular mechanisms.

Submit a Comment

Your email address will not be published. Required fields are marked *

nineteen − two =

[ HIDE/SHOW ]