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Background: Recent investigations provided evidence that herpes simplex virus (HSV-1) and cytomegalovirus (CMV) are reactivated in critically ill individuals. However, at this time, it remains unclear whether these viral infections are of real pathogenetic relevance or represent innocent bystanders., Materials and Methods: In total, 60 patients with septic shock were enrolled. Blood samples and tracheal secretion were collected at the time of sepsis diagnosis (T0) as well as 7 d (T1), 14 d (T2), 21 d (T3), and 28 d (T4) later. The following virologic diagnostics were performed: (1) Viral load of herpes simplex virus type1 (HSV-1) and cytomegalovirus (CMV) in blood samples as well as tracheal secretion using polymerase chain reaction (PCR). (2) Detection of CMV-antigen (pp65) in blood samples using immunofluorescence microscopy. Furthermore plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were evaluated using ELISA-kits., Results: Thirty-one patients (51.7%) were found to be positive for HSV-1, whereas in 16 patients (26.7%) CMV could be identified. Patients with a positive PCR for HSV-1 and/or CMV showed a significantly prolonged length of hospital stay and absolute time of respirator-dependant ventilation. Furthermore, survival curves of patients with a high HSV-1-load (>10E8) in tracheal secretion in comparison with those with a lower HSV-1-load (<10E8) revealed a significantly impaired survival., Conclusions: Viral superinfections with HSV-1 or CMV can frequently be observed in patients with septic shock, especially in those with increased disease severity and a prolonged need for respirator-dependant ventilation. In patients with a viral superinfection morbidity is increased, whereas differences in mortality seem to be dosage-dependant., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Neonatal mice were infected with virus derived from a molecular clone of a laboratory strain of Sindbis virus, TRSB. The resulting acute fatal infection was typified by few if any of the classic hallmarks of encephalitis, very high levels of interferon-alpha/beta (IFNalphabeta), and lesions in the thymus and hematopoietic tissues usually associated with a severe stress response. Infection with an attenuated mutant of TRSB, which harbors a single amino acid change in the E2 surface glycoprotein (TRSBr114), was characterized by encephalitis, reduced mortality, low levels of IFNalphabeta, and no thymic pathology (J. Trgovcich, J. F. Aronson, and R. E. Johnston, 1996, Virology 224, 73-83). Here we report that infection of neonatal mice with TRSB, but not TRSBr114, resulted in induction of high levels of tumor necrosis factor-alpha as well as high and sustained levels of adrenalcorticotropin-releasing hormone and corticosterone. This syndrome of potentially toxic cytokine and stress hormone induction correlates with lethal Sindbis virus infection and constitutes a previously unrecognized aspect of Sindbis virus pathogenesis in mice.