Complement activation in Puumala hantavirus infection correlates with disease severity

Abstract

Introduction. Hantaviruses are important human pathogens that cause clinical diseases characterized by renal and cardiopulmonary manifestations. Their pathogenesis is currently poorly understood. We have studied the role of the complement system in the pathogenesis of Puumala (PUUV) hantavirus infection.

Material and methods. We studied the activation of complement by measuring the terminal complement complex SC5b-9 and complement component C3 and C4 levels in patients with acute PUUV infection. Several laboratory parameters and clinical findings reflecting the severity of PUUV-HFRS were evaluated with regard to complement activation. Results.

The levels of SC5b-9 were significantly increased and C3 decreased in the acute stage as compared to the levels at full recovery (P < 0.001). We found that SC5b-9 levels were higher in patients with chest X-ray abnormalities than in patients with a normal X-ray during the acute stage (P = 0.028). Furthermore, SC5b-9 and C3 levels showed significant correlation with several clinical and laboratory parameters that reflect the severity of the acute PUUV infection.

Conclusions. We showed that the complement system becomes activated via the alternative pathway in the acute stage of PUUV infection and the level of activation correlates with disease severity. The results further suggest that complement activation may contribute to the pathogenesis of acute PUUV infection.

Key words::

• C3
• C4
• complement
• hantavirus
• HFRS
• SC5b-9

Acknowledgements

The skillful technical assistance of Ms Katriina Yli-Nikkilä, Ms Mirja Ikonen, Ms Marita Siren, and Tytti Manni is greatly appreciated.

The study was financially supported by the Medical Research Fund of Tampere University Hospital, the Finnish Kidney Foundation, and the European Commission Project ‘Diagnosis and control of rodent-borne viral zoonoses in Europe’ (QLK2-CT-2002-01358), the Academy of Finland, Sigrid Jusélius Foundation, HUS/EVO grants TYH 7214 and 2008235, and the Helsinki Biomedical Graduate School.

Declaration of interest: The authors report no conflicts of interest.