Role of the feline immunodeficiency virus L-domain in the presence or absence of Gag processing: involvement of ubiquitin and Nedd4-2s ligase in viral egress.
RNA-enveloped viruses bud from infected cells by exploiting the multivesicular body (MVB) pathway. In this context, ubiquitination of structural viral proteins and their direct interaction with cellular factors involved in the MVB biogenesis through short proline rich regions, named late domains (L-domains), are crucial mechanisms. Here we report that, in contrast with the human immunodeficiency virus (HIV), the feline immunodeficiency virus (FIV), a non-primate lentivirus, is strictly dependent for its budding on a "PSAP"-type L-domain, mapping in the carboxy-terminal region of Gag, irrespective of a functional viral protease. Moreover, we provide evidence that FIV egress is related to Gag ubiquitination, that is, linked to the presence of an active L-domain. Finally, although FIV Gag does not contain a PPxY motif, we show that the Nedd4-2s ubiquitin ligase enhances FIV Gag ubiquitination and it is capable to rescue viral mutants lacking a functional L-domain. In conclusion, our data bring to light peculiar aspects of FIV egress, but we also demonstrate that a non-primate lentivirus shares with HIV-1 a novel mechanism of connection to the cellular budding machinery.
Calistri
Arianna
A
Department of Histology, Microbiology and Medical Biotechnologies, Section of Microbiology and Virology, University of Padova, Padova, Italy.
Del Vecchio
Claudia
C
Salata
Cristiano
C
Celestino
Michele
M
Celegato
Marta
M
Göttlinger
Heinrich
H
Palù
Giorgio
G
Parolin
Cristina
C
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002415:Cats; D002460:Cell Line; D056827:Endosomal Sorting Complexes Required for Transport; D015683:Gene Products, gag / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015750:Genes, gag; D015497:HIV-1 / Q000235:genetics / Q000502:physiology; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D000075702:Nedd4 Ubiquitin Protein Ligases; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D019065:Virus Assembly / Q000235:genetics / Q000502:physiology
D056827:Endosomal Sorting Complexes Required for Transport; D015683:Gene Products, gag; D025801:Ubiquitin; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; D044767:Ubiquitin-Protein Ligases
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