scholarly journals Novel Host Protein TBC1D16, a GTPase Activating Protein of Rab5C, Inhibits Prototype Foamy Virus Replication

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun Yan ◽  
Yingcheng Zheng ◽  
Peipei Yuan ◽  
Shanshan Wang ◽  
Song Han ◽  
...  
Keyword(s):  
Latent Infection ◽  
Foamy Virus ◽  
Host Protein ◽  
Rab Gtpase ◽  
Amino Acid Residues ◽  
Restriction Factors ◽  
Antiviral Protein ◽  
Prototype Foamy Virus ◽  
Gtpase Activating Proteins ◽  
Novel Host

Prototype foamy virus (PFV) is a member of the oldest family of retroviruses and maintains lifelong latent infection in the host. The lifelong latent infection of PFV may be maintained by the restriction factors of viral replication in the host. However, the mechanisms involved in PFV latent infection are poorly understood. Here, we found that TBC1D16, a TBC domain-containing protein, is significantly down-regulated after PFV infection. Tre2/Bub2/Cdc16 (TBC) domain-containing proteins function as Rab GTPase-activating proteins (GAPs) and are participates in the progression of some diseases and many signaling pathways. However, whether TBC proteins are involved in PFV replication has not been determined. Here, we found that TBC1D16 is a novel antiviral protein that targets Rab5C to suppress PFV replication. Overexpression TBC1D16 inhibited the transcription and expression of Tas and Gag, and silencing TBC1D16 enhanced the PFV replication. Moreover, the highly conserved amino acid residues R494 and Q531 in the TBC domain of TBC1D16 were essential for inhibiting PFV replication. We also found that TBC1D16 promoted the production of PFV-induced IFN-β and the transcription of downstream genes. These results suggest that TBC1D16 might be the first identified TBC proteins that inhibited PFV replication and the mechanism by which TBC1D16 inhibited PFV replication could provide new insights for PFV latency.

scholarly journals The Late Domain of Prototype Foamy Virus Gag Facilitates Autophagic Clearance of Stress Granules by Promoting Amphisome Formation

2020 ◽  
Vol 94 (7) ◽  
Author(s):  
Yingcheng Zheng ◽  
Guoguo Zhu ◽  
Jun Yan ◽  
Yinglian Tang ◽  
Song Han ◽  
...  
Keyword(s):  
Latent Infection ◽  
Foamy Virus ◽  
Stress Granules ◽  
Autophagic Flux ◽  
Type I ◽  
Type I Ifn ◽  
Antiviral Immune Response ◽  
Prototype Foamy Virus ◽  
Late Domain

ABSTRACT Prototype foamy virus (PFV), a complex retrovirus belonging to Spumaretrovirinae, maintains lifelong latent infection. The maintenance of lifelong latent infection by viruses relies on the repression of the type I interferon (IFN) response. However, the mechanism involving PFV latency, especially regarding the suppression of the IFN response, is poorly understood. Our previous study showed that PFV promotes autophagic flux. However, the underlying mechanism and the role of PFV-induced autophagy in latent infection have not been clarified. Here, we report that the PFV viral structural protein Gag induced amphisome formation and triggered autophagic clearance of stress granules (SGs) to attenuate type I IFN production. Moreover, the late domain (L-domain) of Gag played a central role in Alix recruitment, which promoted endosomal sorting complex required for transport I (ESCRT-I) formation and amphisome accumulation by facilitating late endosome formation. Our data suggest that PFV Gag represses the host IFN response through autophagic clearance of SGs by activating the endosome-autophagy pathway. More importantly, we found a novel mechanism by which a retrovirus inhibits the SG response to repress the type I IFN response. IMPORTANCE Maintenance of lifelong latent infection for viruses relies on repression of the type I IFN response. Autophagy plays a double-edged sword in antiviral immunity. However, the role of autophagy in the regulation of the type I IFN response and the mechanism involving virus-promoted autophagy have not been fully elucidated. SGs are an immune complex associated with the antiviral immune response and are critical for type I IFN production. Autophagic clearance of SGs is one means of degradation of SGs and is associated with regulation of immunity, but the detailed mechanism remains unclear. In this article, we demonstrate that PFV Gag recruits ESCRT-I to facilitate amphisome formation. Our data also suggest that amphisome formation is a critical event for autophagic clearance of SGs and repression of the type I IFN response. More importantly, we found a novel mechanism by which a retrovirus inhibits the SG response to repress the type I IFN response.

scholarly journals An N-terminal domain helical motif of Prototype Foamy Virus Gag with dual functions essential for particle egress and viral infectivity

Retrovirology ◽  
2013 ◽  
Vol 10 (1) ◽  
pp. 45 ◽  
Author(s):  
Juliane Reh ◽  
Annett Stange ◽  
Anne Götz ◽  
Marlene Rönitz ◽  
Arend Große ◽  
...  
Keyword(s):  
Foamy Virus ◽  
Viral Infectivity ◽  
Prototype Foamy Virus ◽  
Terminal Domain ◽  
Dual Functions

scholarly journals Assembly of prototype foamy virus strand transfer complexes on product DNA bypassing catalysis of integration

2012 ◽  
Vol 21 (12) ◽  
pp. 1849-1857 ◽  
Author(s):  
Zhiqi Yin ◽  
Mikalai Lapkouski ◽  
Wei Yang ◽  
Robert Craigie
Keyword(s):  
Foamy Virus ◽  
Strand Transfer ◽  
Prototype Foamy Virus

scholarly journals Prototype Foamy Virus Gag Nuclear Localization: a Novel Pathway among Retroviruses

2011 ◽  
Vol 85 (18) ◽  
pp. 9276-9285 ◽  
Author(s):  
E. Mullers ◽  
K. Stirnnagel ◽  
S. Kaulfuss ◽  
D. Lindemann
Keyword(s):  
Nuclear Localization ◽  
Foamy Virus ◽  
Prototype Foamy Virus

scholarly journals Furin-Mediated Cleavage of the Feline Foamy Virus Env Leader Protein

2004 ◽  
Vol 78 (24) ◽  
pp. 13573-13581 ◽  
Author(s):  
Verena Geiselhart ◽  
Patrizia Bastone ◽  
Tore Kempf ◽  
Martina Schnölzer ◽  
Martin Löchelt
Keyword(s):  
Cleavage Site ◽  
Transmembrane Protein ◽  
Foamy Virus ◽  
Proteolytic Processing ◽  
Signal Peptidase ◽  
Amino Acid Residues ◽  
Furin Cleavage ◽  
Furin Cleavage Site ◽  
Leader Protein ◽  
Distinguishing Features

ABSTRACT The molecular biology of spuma or foamy retroviruses is different from that of the other members of the Retroviridae. Among the distinguishing features, the N-terminal domain of the foamy virus Env glycoprotein, the 16-kDa Env leader protein Elp, is a component of released, infectious virions and is required for particle budding. The transmembrane protein Elp specifically interacts with N-terminal Gag sequences during morphogenesis. In this study, we investigate the mechanism of Elp release from the Env precursor protein. By a combination of genetic, biochemical, and biophysical methods, we show that the feline foamy virus (FFV) Elp is released by a cellular furin-like protease, most likely furin itself, generating an Elp protein consisting of 127 amino acid residues. The cleavage site fully conforms to the rules for an optimal furin site. Proteolytic processing at the furin cleavage site is required for full infectivity of FFV. However, utilization of other furin proteases and/or cleavage at a suboptimal signal peptidase cleavage site can partially rescue virus viability. In addition, we show that FFV Elp carries an N-linked oligosaccharide that is not conserved among the known foamy viruses.

scholarly journals Prototype foamy virus intasome aggregation is mediated by outer protein domains and prevented by protocatechuic acid

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nathan D. Jones ◽  
Randi M. Mackler ◽  
Miguel A. Lopez ◽  
Laura E. Baltierra-Jasso ◽  
Matthew P. Altman ◽  
...  
Keyword(s):  
Protocatechuic Acid ◽  
Foamy Virus ◽  
Protein Domains ◽  
Prototype Foamy Virus

scholarly journals Prototype foamy virus downregulates RelB expression to facilitate viral replication

FEBS Open Bio ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 2137-2148
Author(s):  
Junshi Zhang ◽  
Chenchen Wang ◽  
Xiaopeng Tuo ◽  
Keli Chai ◽  
Yali Xu ◽  
...  
Keyword(s):  
Viral Replication ◽  
Foamy Virus ◽  
Prototype Foamy Virus
Sign in / Sign up

Export Citation Format

Share Document