CD2v Interacts with Adaptor Protein AP-1 during African Swine Fever Infection.
African swine fever virus (ASFV) CD2v protein is believed to be involved in virulence enhancement, viral hemadsorption, and pathogenesis, although the molecular mechanisms of the function of this viral protein are still not fully understood. Here we describe that CD2v localized around viral factories during ASFV infection, suggesting a role in the generation and/or dynamics of these viral structures and hence in disturbing cellular traffic. We show that CD2v targeted the regulatory trans-Golgi network (TGN) protein complex AP-1, a key element in cellular traffic. This interaction was disrupted by brefeldin A even though the location of CD2v around the viral factory remained unchanged. CD2v-AP-1 binding was independent of CD2v glycosylation and occurred on the carboxy-terminal part of CD2v, where a canonical di-Leu motif previously reported to mediate AP-1 binding in eukaryotic cells, was identified. This motif was shown to be functionally interchangeable with the di-Leu motif present in HIV-Nef protein in an AP-1 binding assay. However, we demonstrated that it was not involved either in CD2v cellular distribution or in CD2v-AP-1 binding. Taken together, these findings shed light on CD2v function during ASFV infection by identifying AP-1 as a cellular factor targeted by CD2v and hence elucidate the cellular pathways used by the virus to enhance infectivity.
Virology Department, Centro Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
Daniel
D
Pérez-Núñez
Molecular Design Group, School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Pearse Street, Dublin, Ireland.
Eduardo
E
García-Urdiales
Hospital Gregorio Marañón, Madrid, Spain.
Marta
M
Martínez-Bonet
Virology Department, Centro Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
María L
ML
Nogal
Virology Department, Centro Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
Susana
S
Barroso
Virology Department, Centro Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
Yolanda
Y
Revilla
Virology Department, Centro Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
Ricardo
R
Madrid
D033961:Adaptor Protein Complex 1 / Q000378:metabolism*; D000358:African Swine Fever Virus / Q000378:metabolism / Q000472:pathogenicity*; D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D008264:Macrophages / Q000821:virology; D011485:Protein Binding; D013552:Swine; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
D033961:Adaptor Protein Complex 1; D014764:Viral Proteins