Targeting Sindbis virus-based vectors to Fc receptor-positive cell types

Journal Article · Wed Jul 20 04:00:00 EDT 2005 · Virology

DOI:https://doi.org/10.1016/j.virol.2005.04.039· OSTI ID:20729108

Klimstra, William B ^[1]; Williams, Jacqueline C ^[2]; Ryman, Kate D ^[1]; Heidner, Hans W ^[2]

---

1. Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130 (United States)
2. Department of Biology, University of Texas at San Antonio, 6900 North Loop 1604 West, San Antonio, TX 78249-0662 (United States)

Some viruses display enhanced infection for Fc receptor (FcR)-positive cell types when complexed with virus-specific immunoglobulin (Ig). This process has been termed antibody-dependent enhancement of viral infection (ADE). We reasoned that the mechanism of ADE could be exploited and adapted to target alphavirus-based vectors to FcR-positive cell types. Towards this goal, recombinant Sindbis viruses were constructed that express 1 to 4 immunoglobulin-binding domains of protein L (PpL) as N-terminal extensions of the E2 glycoprotein. PpL is a bacterial protein that binds the variable region of antibody kappa light chains from a range of mammalian species. The recombinant viruses incorporated PpL/E2 fusion proteins into the virion structure and recapitulated the species-specific Ig-binding phenotypes of native PpL. Virions reacted with non-immune serum or purified IgG displayed enhanced binding and ADE for several species-matched FcR-positive murine and human cell lines. ADE required virus expression of a functional PpL Ig-binding domain, and appeared to be Fc{gamma}R-mediated. Specifically, ADE did not occur with Fc{gamma}R-negative cells, did not require active complement proteins, and did not occur on Fc{gamma}R-positive murine cell lines when virions were bound by murine IgG-derived F(ab'){sub 2} fragments.

• OSTI ID: 20729108
• Journal Information: Virology, Journal Name: Virology Journal Issue: 1 Vol. 338; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL CELLS
ANTIBODIES
GLYCOPROTEINS
IMMUNE SERUMS
IMMUNOGLOBULINS
PHENOTYPE
RECEPTORS
VIRUSES