PLASMA-MEMBRANE TARGETING OF CHIMERIC INTRACISTERNAL A-TYPE PARTICLE POLYPROTEINS LEADS TO PARTICLE RELEASE AND SPECIFIC ACTIVATION OF THE VIRAL PROTEINASE
R. Welker et al., PLASMA-MEMBRANE TARGETING OF CHIMERIC INTRACISTERNAL A-TYPE PARTICLE POLYPROTEINS LEADS TO PARTICLE RELEASE AND SPECIFIC ACTIVATION OF THE VIRAL PROTEINASE, Journal of virology, 71(7), 1997, pp. 5209-5217
Retrovirus morphogenesis involves assembly of structural Gag polyprote
ins with subsequent budding from the plasma membrane, followed by prot
eolytic cleavage by the viral proteinase (PR) and extracellular matura
tion to the infectious virion, Intracisternal A-type particles (IAPs)
are defective retroviruses that assemble and bud at the membranes of t
he endoplasmic reticulum (ER), where they remain as immature particles
consisting exclusively of uncleaved polyproteins, To analyze requirem
ents for intracellular polyprotein transport and PR activation, we con
structed deletion and substitution mutations in the IAP gag gene, incl
uding the putative ER-targeting signal, Mutant polyproteins were trans
ported to various intracellular locations, including the nucleus, the
cytoplasm, the ER, and the plasma membrane, Interestingly, assembly of
capsid-like particle structures occurred at almost all sites, However
, only those polyproteins transported to the plasma membrane were effi
ciently and specifically cleaved by viral PR, with cleavage occurring
predominantly within the virus particle. Thus, at least in the experim
ental system presented here, retroviral particle assembly can occur at
almost any location within the cell, while polyprotein processing and
, consequently, virion maturation are confined to a specific cellular
site, These results suggest that a factor restricted to the plasma mem
brane is required to trigger PR activation and maturation of infectiou
s retroviruses.