Vaccinia virus p37 interacts with host proteins associated with LE-derived transport vesicle biogenesis.
BACKGROUND
Proteins associated with the late endosome (LE) appear to play a central role in the envelopment of a number of taxonomically diverse viruses. How viral proteins interact with LE-associated proteins to facilitate envelopment is not well understood. LE-derived transport vesicles form through the interaction of Rab9 GTPase with cargo proteins, and TIP47, a Rab9-specific effector protein. Vaccinia virus (VV) induces a wrapping complex derived from intracellular host membranes to envelope intracellular mature virus particles producing egress-competent forms of virus.


RESULTS
We show that VV p37 protein associates with TIP47-, Rab9-, and CI-MPR-containing membranes. Mutation of a di-aromatic motif in p37 blocks association with TIP47 and inhibits plaque formation. ST-246, a specific inhibitor of p37 function, inhibits these interactions and also blocks wrapped virus particle formation. Vaccinia virus expressing p37 variants with reduced ST-246 susceptibility associates with Rab9 and co-localizes with CI-MPR in the presence and absence of compound.


CONCLUSIONS
These results suggest that p37 localizes to the LE and interacts with proteins associated with LE-derived transport vesicle biogenesis to facilitate assembly of extracellular forms of virus.
Chen
Yali
Y
SIGA Technologies Inc, Corvallis, Oregon 97333, USA. ychen@siga.com
Honeychurch
Kady M
KM
Yang
Guang
G
Byrd
Chelsea M
CM
Harver
Chris
C
Hruby
Dennis E
DE
Jordan
Robert
R
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism / Q000821:virology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D000070796:Perilipin-3; D011257:Pregnancy Proteins / Q000378:metabolism*; D011485:Protein Binding; D017527:Receptor, IGF Type 2; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism* / Q000821:virology; D014615:Vaccinia / Q000378:metabolism* / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C038196:PLIN3 protein, human; D000070796:Perilipin-3; D011257:Pregnancy Proteins; D017527:Receptor, IGF Type 2; D018160:Receptors, Cytoplasmic and Nuclear; D033921:Vesicular Transport Proteins; D014759:Viral Envelope Proteins; C034304:cation-dependent mannose-6-phosphate receptor; C084759:p37 protein, Vaccinia virus; C079856:RAB9A protein, human; D020691:rab GTP-Binding Proteins