TY - JOUR
T1 - Interaction of extremophilic archaeal viruses with human and mouse complement system and viral biodistribution in mice
AU - Wu, Linping
AU - Uldahl, Kristine Buch
AU - Chen, Fangfang
AU - Benasutti, Halli
AU - Logvinski, Deborah
AU - Vu, Vivian
AU - Banda, Nirmal K.
AU - Peng, Xu
AU - Simberg, Dmitri
AU - Moghimi, Seyed Moein
PY - 2017/10
Y1 - 2017/10
N2 - Archaeal viruses offer exceptional biophysical properties for modification and exploration of their potential in bionanotechnology, bioengineering and nanotherapeutic developments. However, the interaction of archaeal viruses with elements of the innate immune system has not been explored, which is a necessary prerequisite if their potential for biomedical applications to be realized. Here we show complement activation through lectin (via direct binding of MBL/MASPs) and alternative pathways by two extremophilic archaeal viruses (Sulfolobus monocaudavirus 1 and Sulfolobus spindle-shaped virus 2) in human serum. We further show some differences in initiation of complement activation pathways between these viruses. Since, Sulfolobus monocaudavirus 1 was capable of directly triggering the alternative pathway, we also demonstrate that the complement regulator factor H has no affinity for the viral surface, but factor H deposition is purely C3-dependent. This suggests that unlike some virulent pathogens Sulfolobus monocaudavirus 1 does not acquire factor H for protection. Complement activation with Sulfolobus monocaudavirus 1 also proceeds in murine sera through MBL-A/C as well as factor D-dependent manner, but C3 deficiency has no overall effect on viral clearance by organs of the reticuloendothelial system on intravenous injection. However, splenic deposition was significantly higher in C3 knockout animals compared with the corresponding wild type mice. We discuss the potential application of these viruses in biomedicine in relation to their complement activating properties.
AB - Archaeal viruses offer exceptional biophysical properties for modification and exploration of their potential in bionanotechnology, bioengineering and nanotherapeutic developments. However, the interaction of archaeal viruses with elements of the innate immune system has not been explored, which is a necessary prerequisite if their potential for biomedical applications to be realized. Here we show complement activation through lectin (via direct binding of MBL/MASPs) and alternative pathways by two extremophilic archaeal viruses (Sulfolobus monocaudavirus 1 and Sulfolobus spindle-shaped virus 2) in human serum. We further show some differences in initiation of complement activation pathways between these viruses. Since, Sulfolobus monocaudavirus 1 was capable of directly triggering the alternative pathway, we also demonstrate that the complement regulator factor H has no affinity for the viral surface, but factor H deposition is purely C3-dependent. This suggests that unlike some virulent pathogens Sulfolobus monocaudavirus 1 does not acquire factor H for protection. Complement activation with Sulfolobus monocaudavirus 1 also proceeds in murine sera through MBL-A/C as well as factor D-dependent manner, but C3 deficiency has no overall effect on viral clearance by organs of the reticuloendothelial system on intravenous injection. However, splenic deposition was significantly higher in C3 knockout animals compared with the corresponding wild type mice. We discuss the potential application of these viruses in biomedicine in relation to their complement activating properties.
KW - Complement system
KW - Mannose-binding lectin
KW - Nano-biotechnology
KW - Reticuloendothelial system
KW - Sulfolobus monocaudavirus 1
KW - Sulfolobus spindle-shaped virus 2
UR - http://www.scopus.com/inward/record.url?scp=85028343853&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2017.08.009
DO - 10.1016/j.molimm.2017.08.009
M3 - Journal article
C2 - 28846925
AN - SCOPUS:85028343853
SN - 0161-5890
VL - 90
SP - 273
EP - 279
JO - Molecular Immunology
JF - Molecular Immunology
ER -