Effects of herpes simplex virus type 1 infection on immune functions of human neutrophils


Dr Yen-Ting Chen, Department of Dentistry, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St., Pei-Tou, Taipei 11221, Taiwan
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Hung S-L, Chiang H-H, Wu C-Y, Hsu M-J, Chen Y-T. Effects of herpes simplex virus type 1 infection on immune functions of human neutrophils. J Periodont Res 2012; 47: 635–644. © 2012 John Wiley & Sons A/S

Background and Objective:  Herpesviruses may play roles in the development of periodontal diseases. This study analyzed the effects of herpes simplex virus type 1 (HSV-1) infection on neutrophil function. The effects of lipopolysaccharide (LPS) from the periodontal pathogen, Porphyromonas gingivalis, during HSV-1 infection were also determined.

Material and Methods:  Purified HSV-1 was pretreated with buffer containing no serum, with HSV-1 immunoglobulin G (IgG)-positive serum (HSV-1 antiserum) or with control serum. Neutrophils were mock-infected or infected with the pretreated HSV-1. Viral binding and phagosome formation were detected using immunostaining. Intracellular reactive oxygen species (ROS) were determined using 2′,7′-dichlorofluorescin diacetate and fluorometry. Leukotriene B4 (LTB4) and interleukin-8 (IL-8) were detected using enzyme immunoassays. Release of matrix metalloproteinase-9 (MMP-9) was examined using gelatin zymography. Phosphorylation of Akt/glycogen synthase kinase-3 (GSK-3) was determined using western blotting.

Results:  HSV-1 bound directly to neutrophils and enhanced the release of MMP-9. HSV-1 immune complexes, formed in the HSV-1 antiserum, bound neutrophils and induced the formation of early phagosome more effectively than did HSV-1 alone. The relative levels of ROS and phosphorylation of Akt/GSK-3 were increased significantly in neutrophils after infection with HSV-1 immune complexes. Infection with HSV-1 and HSV-1 immune complexes also stimulated the production of inflammatory mediators, LTB4 and IL-8. Moreover, LPS enhanced the HSV-1-stimulatory production of IL-8.

Conclusion:  This study demonstrated differences in neutrophils infected with HSV-1 alone or with HSV-1 immune complexes, suggesting that opsonization of HSV-1 might enhance its effects on neutrophils. The in vitro findings suggest that HSV-1 infection may induce the inflammatory response and affect periodontal health.