Involvement of CD16 in antibody-dependent enhancement of porcine reproductive and respiratory syndrome virus infection.
The immunological effect of porcine reproductive and respiratory syndrome disease virus (PRRSV) vaccines is thought to be influenced by a variety of host factors, in which antibody-dependent enhancement (ADE) of infection is one crucial factor. Here, we assessed the mechanism of ADE of PRRSV infection. First, we found that subneutralizing serum could induce ADE of PRRSV infection in porcine alveolar macrophages (PAMs). Quantitative PCR, Western blotting and flow cytometry revealed that CD16 is the most abundant Fcγ receptor (FcγR) expressed on the surface of PAMs; thus, the role of CD16 in ADE of PRRSV infection was examined in PAMs. By using functional blocking antibodies, we demonstrated that CD16 is involved in enhanced virus production in PRRSV-antibody immune complex-infected PAMs. Because PAMs co-express different FcγR isoforms, we evaluated the effects of CD16 in FcγR-non-bearing cells by transfection. Using these engineered cells, we found that CD16 could specifically bind to the PRRSV-antibody immune complex and subsequently mediate internalization of the virus, resulting in the generation of progeny virus. We also showed that efficient expression of CD16 required association of the FcR γ-chain. Together, our findings provide significant new insights into PRRSV infection, which can be enhanced by CD16-mediated PRRSV-antibody immune complexes. This CD16-mediated ADE may induce a shift in PRRSV tropism towards CD16-expressing cells, distributing virus to more organs during virus infection.
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China.
Weihong
W
Gu
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China.
Longjun
L
Guo
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China.
Haidong
H
Yu
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China.
Junwei
J
Niu
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China.
Mingming
M
Huang
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China.
Xiaolei
X
Luo
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China.
Ren
R
Li
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China.
Zhijun
Z
Tian
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China.
Li
L
Feng
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China.
Yue
Y
Wang
D000818:Animals; D019067:Antibody-Dependent Enhancement; D000936:Antigen-Antibody Complex / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D005434:Flow Cytometry; D016676:Macrophages, Alveolar / Q000276:immunology / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000502:physiology*; D011485:Protein Binding; D060888:Real-Time Polymerase Chain Reaction; D017452:Receptors, IgG / Q000378:metabolism*; D013552:Swine; D053585:Virus Attachment; D053586:Virus Internalization
D000936:Antigen-Antibody Complex; D017452:Receptors, IgG