6533b86ffe1ef96bd12ce8bc

RESEARCH PRODUCT

ESCRT Requirements for Murine Leukemia Virus Release

Reinhild PrangeChristina Bartusch

subject

0301 basic medicineMLV; VLPs; retroviral budding; viral late domain; ESCRT; MVB pathway; CHMP1AEndosomevirusesGenetic Vectorslcsh:QR1-502CHMP1AGene ExpressionGene Products gagMLVmacromolecular substanceslcsh:MicrobiologyArticleESCRTCell LineESCRTMice03 medical and health sciencesviral late domainMVB pathwayVirologyGene OrderMurine leukemia virusAnimalsHumansVLPsTSG101Viral sheddingVirus Releaseretroviral buddingGammaretrovirusBuddingEndosomal Sorting Complexes Required for Transportbiologybiochemical phenomena metabolism and nutritionbiology.organism_classificationVirologyVirus ReleaseLeukemia Virus Murine030104 developmental biologyInfectious DiseasesGene Knockdown TechniquesRetroviridae Infections

description

The Murine Leukemia Virus (MLV) is a gammaretrovirus that hijack host components of the endosomal sorting complex required for transport (ESCRT) for budding. To determine the minimal requirements for ESCRT factors in MLV viral and viral-like particles (VLP) release, an siRNA knockdown screen of ESCRT(-associated) proteins was performed in MLV-producing human cells. We found that MLV VLPs and virions primarily engage the ESCRT-I factor Tsg101 and marginally the ESCRT-associated adaptors Nedd4-1 and Alix to enter the ESCRT pathway. Conversely, the inactivation of ESCRT-II had no impact on VLP and virion egress. By analyzing the effects of individual ESCRT-III knockdowns, VLP and virion release was profoundly inhibited in CHMP2A- and CHMP4B-knockdown cells. In contrast, neither the CHMP2B and CHMP4A isoforms nor CHMP3, CHMP5, and CHMP6 were found to be essential. In case of CHMP1, we unexpectedly observed that the CHMP1A isoform was specifically required for virus budding, but dispensable for VLP release. Hence, MLV utilizes only a subset of ESCRT factors, and viral and viral-like particles differ in ESCRT-III factor requirements.

yearjournalcountryeditionlanguage
2016-02-29Viruses
https://doi.org/10.3390/v8040103