Acquisition of complement resistance through incorporation of CD55/decay-accelerating factor into viral particles bearing baculovirus GP64.

Abstract

A major obstacle to gene transduction by viral vectors is inactivation by human complement in vivo. One way to overcome this is to incorporate complement regulatory proteins, such as CD55/decay accelerating factor (DAF), into viral particles. Lentivirus vectors pseudotyped with the baculovirus envelope protein GP64 have been shown to acquire more potent resistance to serum inactivation and longer transgene expression than those pseudotyped with the vesicular stomatitis virus (VSV) envelope protein G. However, the molecular mechanisms underlying resistance to serum inactivation in pseudotype particles bearing the GP64 have not been precisely elucidated. In this study, we generated pseudotype and recombinant VSVs bearing the GP64. Recombinant VSVs generated in human cell lines exhibited the incorporation of human DAF in viral particles and were resistant to serum inactivation, whereas those generated in insect cells exhibited no incorporation of human DAF and were sensitive to complement inactivation. The GP64 and human DAF were detected on the detergent-resistant membrane and were coprecipitated by immunoprecipitation analysis. A pseudotype VSV bearing GP64 produced in human DAF knockdown cells reduced resistance to serum inactivation. In contrast, recombinant baculoviruses generated in insect cells expressing human DAF or carrying the human DAF gene exhibited resistance to complement inactivation. These results suggest that the incorporation of human DAF into viral particles by interacting with baculovirus GP64 is involved in the acquisition of resistance to serum inactivation.

• Authors: Yuuki Kaname, Hideki Tani, Chikako Kataoka, Mai Shiokawa, Shuhei Taguwa, Takayuki Abe, Kohji Moriishi, Taroh Kinoshita, Yoshiharu Matsuura
• Journal: Journal of virology (J Virol) Vol. 84 Issue 7 Pg. 3210-9 (Apr 2010) ISSN: 1098-5514 [Electronic] United States
• PMID: 20071581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD55 Antigens
• Complement Inactivator Proteins
• Viral Fusion Proteins

Topics

• Animals
• Baculoviridae (genetics)
• Bombyx
• CD55 Antigens (genetics, physiology)
• Cells, Cultured
• Complement Inactivator Proteins (genetics, physiology)
• Genetic Therapy
• Glycosylation
• Humans
• Spodoptera
• Vesicular stomatitis Indiana virus (genetics)
• Viral Fusion Proteins (genetics)
• Virion (physiology)