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A neutrophil-derived antiviral protein: induction requirements and biological properties
H B Ohmann1, M Campos, D R Fitzpatrick
1Veterinary Infectious Disease Organization, Saskatoon, Saskatchewan, Canada.
Abstract:
Polymorphonuclear neutrophilic granulocytes (PMN) have been implicated as playing a role in antiviral defense. In addition to having phagocytic and cytotoxic activities, PMN may produce an antiviral substance with interferon (IFN)-like activity. The product, for which the name polyferon (PF) has been coined, is produced upon direct encounter of PMN with bovine herpesvirus 1 (BHV-1)-infected bovine cells or membranes thereof. Exposure to purified virus only does not induce PF. The intimate interaction between PMN and the membranes was also revealed by electron microscopy studies. Bovine cells infected with herpes simplex virus type 1 could also induce PF production by bovine PMN, whereas cells infected with BHV-2, herpes simplex virus type 2, equine herpesvirus 1, bovine respiratory syncytial virus, bovine viral diarrhea virus, or parainfluenza virus 3 were unable to do so. Results obtained in experiments using transfected cells expressing BHV-1 glycoproteins as well as blocking experiments using BHV-1 glycoprotein-monospecific antibodies suggested that a combination of both viral product(s) and host cell factor(s) unique to bovine cells is required for induction of PF production by PMN. PF, which appeared in detectable amounts 12 to 18 h after exposure of PMN to the appropriate inducer, could not be neutralized by antibodies to bovine IFN-alpha, -beta, and -gamma. PF may nevertheless belong to the IFN family of proteins, as indicated by its ability to induce 2',5'-oligoadenyl synthetase in various cell types that are responsive to bovine IFNs and by its antiviral spectrum. It does, however, differ from the other cytokines in most immunological characteristics tested so far, including major histocompatibility complex class II antigen induction, cell migration, and cytotoxicity.
Insights
Polymorphonuclear neutrophils produce a novel antiviral substance, polyferon, upon interaction with infected cells. This substance exhibits interferon-like activity but has distinct immunological characteristics.
Area of Science:
- Veterinary Virology
- Immunology
- Cell Biology
Background:
- Polymorphonuclear neutrophilic granulocytes (PMN) are known for phagocytic and cytotoxic roles.
- PMN may produce antiviral substances with interferon (IFN)-like activity.
Purpose of the Study:
- To investigate the production of a novel antiviral substance, termed polyferon (PF), by bovine PMN.
- To characterize the induction and properties of PF.
Main Methods:
- Exposure of bovine PMN to infected cells and purified viruses.
- Electron microscopy to study PMN-cell interactions.
- Experiments with transfected cells and blocking antibodies.
- Assays for antiviral activity and IFN-like properties.
Main Results:
- PF production was induced by bovine herpesvirus 1 (BHV-1)-infected cells, not by purified BHV-1.
- Bovine PMN produced PF when interacting with cells infected by BHV-1 and herpes simplex virus type 1, but not other tested viruses.
- PF induction required viral products and bovine-specific host cell factors.
- PF exhibited IFN-like activity (inducing 2',5'-oligoadenyl synthetase) but differed immunologically from known bovine IFNs.
Conclusions:
- Bovine PMN produce a unique antiviral substance, PF, upon specific cellular interactions.
- PF represents a distinct antiviral factor, potentially related to the IFN family but with unique characteristics.
- The findings highlight a novel aspect of innate antiviral immunity involving PMN.