TY - JOUR
T1 - Inactivation of enveloped virus by laser-driven protein aggregation
AU - Tsen, Shaw Wei D
AU - Chapa, Travis
AU - Beatty, Wandy
AU - Tsen, Kong-Thon
AU - Yu, Dong
AU - Achilefua, Samuel
N1 - Funding Information:
We would like to thank Irina Sorokina (Midwest Bio Services LLC, Overland Park, Kansas) for mass spectrometry analysis. This work was supported in part by the Mallinckrodt Institute of Radiology Development Fund, NIH Grant R33 CA123537, NHLBI Ruth L. Kirschstein NRSA F30 Grant HL116183-01 (Shaw-Wei Tsen), and Public Health Service Grant R01CA120768 (Dong Yu).
PY - 2012/12
Y1 - 2012/12
N2 - Ultrafast lasers in the visible and near-infrared range have emerged as a potential new method for pathogen reduction of blood products and pharmaceuticals. However, the mechanism of enveloped virus inactivation by this method is unknown. We report the inactivation as well as the molecular and structural effects caused by visible (425 nm) femtosecond laser irradiation on murine cytomegalovirus (MCMV), an enveloped, double-stranded DNA virus. Our results show that laser irradiation (1) caused a 5-log reduction in MCMV titer, (2) did not cause significant changes to the global structure of MCMV virions including membrane and capsid, as assessed by electron microscopy, (3) produced no evidence of double-strand breaks or crosslinking in MCMV genomic DNA, and (4) caused selective aggregation of viral capsid and tegument proteins. We propose a model in which ultrafast laser irradiation induces partial unfolding of viral proteins by disrupting hydrogen bonds and/or hydrophobic interactions, leading to aggregation of closely associated viral proteins and inactivation of the virus. These results provide new insight into the inactivation of enveloped viruses by visible femtosecond lasers at the molecular level, and help pave the way for the development of a new ultrafast laser technology for pathogen reduction.
AB - Ultrafast lasers in the visible and near-infrared range have emerged as a potential new method for pathogen reduction of blood products and pharmaceuticals. However, the mechanism of enveloped virus inactivation by this method is unknown. We report the inactivation as well as the molecular and structural effects caused by visible (425 nm) femtosecond laser irradiation on murine cytomegalovirus (MCMV), an enveloped, double-stranded DNA virus. Our results show that laser irradiation (1) caused a 5-log reduction in MCMV titer, (2) did not cause significant changes to the global structure of MCMV virions including membrane and capsid, as assessed by electron microscopy, (3) produced no evidence of double-strand breaks or crosslinking in MCMV genomic DNA, and (4) caused selective aggregation of viral capsid and tegument proteins. We propose a model in which ultrafast laser irradiation induces partial unfolding of viral proteins by disrupting hydrogen bonds and/or hydrophobic interactions, leading to aggregation of closely associated viral proteins and inactivation of the virus. These results provide new insight into the inactivation of enveloped viruses by visible femtosecond lasers at the molecular level, and help pave the way for the development of a new ultrafast laser technology for pathogen reduction.
KW - Murine cytomegalovirus
KW - Pathogen inactivation
KW - Pathogen reduction
KW - Ultrafast lasers
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U2 - 10.1117/1.JBO.17.12.128002
DO - 10.1117/1.JBO.17.12.128002
M3 - Article
C2 - 23224114
AN - SCOPUS:84878282774
SN - 1083-3668
VL - 17
JO - Journal of biomedical optics
JF - Journal of biomedical optics
IS - 12
M1 - 128002
ER -