Structure of a Spumaretrovirus Gag Central Domain Reveals an Ancient Retroviral Capsid.

Abstract:

:The Spumaretrovirinae, or foamy viruses (FVs) are complex retroviruses that infect many species of monkey and ape. Despite little sequence homology, FV and orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking and membrane targeting. However, there is a paucity of structural information for FVs and it is unclear how disparate FV and orthoretroviral Gag molecules share the same function. To probe the functional overlap of FV and orthoretroviral Gag we have determined the structure of a central region of Gag from the Prototype FV (PFV). The structure comprises two all α-helical domains NtDCEN and CtDCEN that although they have no sequence similarity, we show they share the same core fold as the N- (NtDCA) and C-terminal domains (CtDCA) of archetypal orthoretroviral capsid protein (CA). Moreover, structural comparisons with orthoretroviral CA align PFV NtDCEN and CtDCEN with NtDCA and CtDCA respectively. Further in vitro and functional virological assays reveal that residues making inter-domain NtDCEN-CtDCEN interactions are required for PFV capsid assembly and that intact capsid is required for PFV reverse transcription. These data provide the first information that relates the Gag proteins of Spuma and Orthoretrovirinae and suggests a common ancestor for both lineages containing an ancient CA fold.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Ball NJ,Nicastro G,Dutta M,Pollard DJ,Goldstone DC,Sanz-Ramos M,Ramos A,Müllers E,Stirnnagel K,Stanke N,Lindemann D,Stoye JP,Taylor WR,Rosenthal PB,Taylor IA

doi

10.1371/journal.ppat.1005981

subject

Has Abstract

pub_date

2016-11-09 00:00:00

pages

e1005981

issue

11

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-16-01565

journal_volume

12

pub_type

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