Severe human
infection with Hantavirus is characterized by high
fever, cold
chills,
thrombocytopenia, arterial
hypotension,
acute renal failure, and/or
adult respiratory distress syndrome (ARDS)-like pulmonary involvement, but the
clinical course varies greatly between individuals. We investigated whether genetically determined differences in
tumor necrosis factor (
TNF)-alpha production can influence the severity of Hantavirus disease. We studied a
TNF-alpha single-
nucleotide promoter polymorphism (SNP) at position -238 (a
guanine [G]-to-
adenine [A] transition) and ex vivo
TNF-alpha production in a recall study of 36 Belgian patients who had a serologically proven form of Puumala virus-induced
Hantavirus infection with the kidney as main target organ. In our study, the highest
creatinine levels were found in patients with the lowest ex vivo
TNF-alpha production.
Creatinine levels correlated inversely with
TNF-alpha production (R = -0.35, p < 0.05). The number of thrombocytes was significantly lower in patients with the GA-238 genotype (low
TNF-alpha producers) compared with patients with the GG-238 genotype. In our study, genetically determined low production of
TNF-alpha was associated with some parameters indicating a more severe
clinical course of Puumala
Hantavirus infection in humans, possibly by impaired activation of
TNF-alpha-dependent
antiviral mechanisms, which could in turn result in decreased clearance of Hantavirus.