Impact of myristoyl switch-triggered matrix domain cleavage on the late stage of Mason-Pfizer monkey virus life cycle

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F25%3A43932634" target="_blank" >RIV/60461373:22340/25:43932634 - isvavai.cz</a>

Alternative codes found

RIV/60461373:22330/25:43932634

Result on the web

—

DOI - Digital Object Identifier

—

Result language

angličtina

Original language name

Impact of myristoyl switch-triggered matrix domain cleavage on the late stage of Mason-Pfizer monkey virus life cycle

Original language description

Retroviral particles formed during the late phase of the viral life cycle must undergo maturation to become infectious. This process involves proteolytic cleavage of the Gag and Gag-Pol polyproteins by the viral protease at specific cleavage sites. In C-type retroviruses like HIV, which assemble at the plasma membrane (PM), maturation could be triggered by PM interaction and protease dimerization during particle assembly. In contrast, D-type retroviruses such as Mason-Pfizer monkey virus (M-PMV) assemble in the cytoplasm. Immature particles are transported to the PM in an unprocessed state, where budding and maturation occur. Thus, maturation must be tightly regulated, and protease dimerization alone is unlikely to trigger the maturation process.We previously showed that in vitro cleavage of the myristoylated matrix (MA) domain from the downstream phosphoprotein (PP) domain of Gag by M-PMV protease is induced by MA-liposome interaction. This cleavage is facilitated by a myristoyl switch-triggered conformational change at the cleavage site.To assess the role of this cleavage in viral maturation in vivo, we generated vectors encoding noninfectious particles with amino acid substitutions affecting MA myristoylation, myristoyl switch, or MA-PP cleavage. β-branched amino acids, typically used to inhibit HIV-1 protease, did not block MA cleavage in M-PMV. However, M100P, A101K and A102K substitutions effectively prevented cleavage. Mutant particles were produced in HEK293T cells, and the effects on viral maturation were evaluated.

Czech name

—

Czech description

—

Type

O - Miscellaneous

CEP classification

—

OECD FORD branch

10607 - Virology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů