Arenavirus Z-glycoprotein association requires Z myristoylation but not functional RING or late domains.
Generation of infectious arenavirus-like particles requires the virus RING finger Z protein and surface glycoprotein precursor (GPC) and the correct processing of GPC into GP1, GP2, and a stable signal peptide (SSP). Z is the driving force of arenavirus budding, whereas the GP complex (GPc), consisting of hetero-oligomers of SSP, GP1, and GP2, forms the viral envelope spikes that mediate receptor recognition and cell entry. Based on the roles played by Z and GP in the arenavirus life cycle, we hypothesized that Z and the GPc should interact in a manner required for virion formation. Here, using confocal microscopy and coimmunoprecipitation assays, we provide evidence for subcellular colocalization and biochemical interaction, respectively, of Z and the GPc. Our results from mutation-function analysis reveal that Z myristoylation, but not the Z late (L) or RING domain, is required for Z-GPc interaction. Moreover, Z interacted directly with SSP in the absence of other components of the GPc. We obtained similar results with Z and GPC from the prototypical arenavirus lymphocytic choriomeningitis virus and the hemorrhagic fever arenavirus Lassa fever virus.
Capul
Althea A
AA
Molecular and Integrative Neuroscience Department, Scripps Research Institute, 10550 North Torrey Pines Road, IMM-6, La Jolla, CA 92037, USA.
Perez
Mar
M
Burke
Emily
E
Kunz
Stefan
S
Buchmeier
Michael J
MJ
de la Torre
Juan C
JC
D000818:Animals; D018050:Arenavirus / Q000502:physiology*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D003593:Cytoplasm / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins; D018613:Microscopy, Confocal; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*; D019065:Virus Assembly / Q000502:physiology*
D002352:Carrier Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D016601:RNA-Binding Proteins; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C479900:glycoprotein C, lymphocytic choriomeningitis virus; C117526:p11 Z protein, Lymphocytic choriomeningitis virus; C487631:protein Z, Lassa virus