TY - JOUR
T1 - Dissecting the Components of Sindbis Virus from Arthropod and Vertebrate Hosts
T2 - Implications for Infectivity Differences
AU - Dunbar, Carmen A.
AU - Rayaprolu, Vamseedhar
AU - Wang, Joseph C.Y.
AU - Brown, Christopher J.
AU - Leishman, Emma
AU - Jones-Burrage, Sara
AU - Trinidad, Jonathan C.
AU - Bradshaw, Heather B.
AU - Clemmer, David E.
AU - Mukhopadhyay, Suchetana
AU - Jarrold, Martin F.
N1 - Funding Information:
We gratefully acknowledge the support of the National Science Foundation through grant numbers CHE-1531823 (M.F.J.) and DA00668 (H.B.B.) and the National Institutes of Health through grant number R01 GM117207-01 (D.E.C.). We also gratefully acknowledge the support of the Indiana University Office of the Vice President for Research (S.M.).
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/6/14
Y1 - 2019/6/14
N2 - Sindbis virus (SINV) is an enveloped, single-stranded RNA virus, which is transmitted via mosquitos to a wide range of vertebrate hosts. SINV produced by vertebrate, baby hamster kidney (BHK) cells is more than an order of magnitude less infectious than SINV produced from mosquito (C6/36) cells. The cause of this difference is poorly understood. In this study, charge detection mass spectrometry was used to determine the masses of intact SINV particles isolated from BHK and C6/36 cells. The measured masses are substantially different: 52.88 MDa for BHK derived SINV and 50.69 MDa for C6/36 derived. Further analysis using several mass spectrometry-based methods and biophysical approaches indicates that BHK derived SINV has a substantially higher mass than C6/36 derived because in the lipid bilayer, there is a higher portion of lipids containing long chain fatty acids. The difference in lipid composition could influence the organization of the lipid bilayer. As a result, multiple stages of the viral lifecycle may be affected including assembly and budding, particle stability during transmission, and fusion events, all of which could contribute to the differences in infectivity.
AB - Sindbis virus (SINV) is an enveloped, single-stranded RNA virus, which is transmitted via mosquitos to a wide range of vertebrate hosts. SINV produced by vertebrate, baby hamster kidney (BHK) cells is more than an order of magnitude less infectious than SINV produced from mosquito (C6/36) cells. The cause of this difference is poorly understood. In this study, charge detection mass spectrometry was used to determine the masses of intact SINV particles isolated from BHK and C6/36 cells. The measured masses are substantially different: 52.88 MDa for BHK derived SINV and 50.69 MDa for C6/36 derived. Further analysis using several mass spectrometry-based methods and biophysical approaches indicates that BHK derived SINV has a substantially higher mass than C6/36 derived because in the lipid bilayer, there is a higher portion of lipids containing long chain fatty acids. The difference in lipid composition could influence the organization of the lipid bilayer. As a result, multiple stages of the viral lifecycle may be affected including assembly and budding, particle stability during transmission, and fusion events, all of which could contribute to the differences in infectivity.
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U2 - 10.1021/acsinfecdis.8b00356
DO - 10.1021/acsinfecdis.8b00356
M3 - Article
C2 - 30986033
AN - SCOPUS:85065068591
SN - 2373-8227
VL - 5
SP - 892
EP - 902
JO - ACS Infectious Diseases
JF - ACS Infectious Diseases
IS - 6
ER -
