Pathogenesis of viral infections of the fetus.
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Potent sheep anti-mouse interferon globulin has been used to determine the role of virus-induced interferon in mouse hepatitis virus type 3-infected susceptible (C57BL/6), semiresistant (C3H/He), and resistant (A/J) strains of mice. Injection of anti-interferon globulin accelerated the onset of death in C57BL/6 mice, induced almost 100% mortality in C3H/He mice that usually do not die of acute disease, and caused death in 4- and 6-week-old A/J mice, but not in older mice. We conclude that interferon is an important host defense factor in the initial response of different strains of mice to MHV-3 infection. Other factors, however, such as the capacity of macrophages to restrict viral multiplication probably underlie the genetically determined susceptibility or resistance of mice to MHV-3 infection.
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Leucocyte populations from rainbow trout subjected to experimental viral haemorrhagic septicaemia virus (VHSV) infections under in vivo and in vitro conditions were analysed by flow cytometry. Quantitative analysis shows that only a low percentage of the leucocytes support viral replication. Lymphocytes, compared with monocytes granulocytes and macrophages, are the least susceptible sub-population. A decrease in the amount of the phagocytic activity was observed after the cells were infected with VHSV. Obvious modifications were observed through dot plot profiles in the composition of the cell sub-populations and in the cell morphology. In addition to a direct effect of VHSV on the macrophages, a systemic effect is produced. This could also be related to the stress induced by the experimental infection process.
502 patients with acute viral hepatitis B were examined for blood levels of hydrocortisone and insulin, blood proteolytic systems, proteinase inhibitors, acute phase proteins. Most of the biochemical reactions promoted compensation and adaptation processes inhibiting the disease progression. In severe and progressive hepatitides biochemical mechanisms of adaptation are impaired. This entails pathogenetic implications.
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Progressive multifocal leukoencephalopathy is an important viral opportunistic infection of oligodendrocytes leading to direct demyelination. Virus is likely disseminated to the brain via the blood. However, the timing of that dissemination with relationship to clinical disease is unknown. Important clues about viral pathogenesis have been learned by applying molecular in situ techniques to diseased brain. The oligodendrocyte is the primary target for JC virus infection, and its death is the primary reason for demyelination. Bizarre astrocytes show limited viral DNA replication but are abortively infected. Although lymphoid organs can be infected by JC virus, there is no definitive evidence that lymphoid cells carry virus into the brain at the time of immunosuppression. JC virus may be reactivated from a latent state in both the brain and in non-central nervous system (CNS) organs at the time of immunosuppression, leading to clinical disease. Future sensitive in situ studies will likely resolve controversies about pathogenesis.
Foot and mouth disease virus (FMDV) is a picornavirus that causes an acute vesicular disease of cloven-hoofed animals. This virus continues to be a threat to livestock worldwide with outbreaks causing severe economic losses. The present study shows an analysis of immune system phenotype and function during the acute phase of FMDV infection in swine. In the first days of infection, a significant lymphopenia is observed that involves all T cell subsets, CD4(+), CD8(+), and CD4(+)/CD8(+). This marked lymphopenia is not a result of active infection of PBMC with the virus. Further, the response of residual peripheral blood T cells to the mitogen, Concanavalin A (ConA) is significantly reduced and occasionally eliminated. Animals usually resolve clinical signs of disease and develop antigen specific T cell responses to the virus and recover ConA reactivity. These characteristics of acute phase infection likely play an important role in viral pathogenesis, propagation and shedding of viral particles and may be targeted as a way of improving vaccine formulations.
The pathogenic mechanism of infections is a complicated but important scientific theme that is now attracting great attention because of its association with host-derived as well as microbial factors. Recent advances in free radical research revealed that reactive oxygen and nitrogen oxide species such as superoxide (O(2)(-)) and nitric oxide (NO) play a leading role in the pathogenesis of infections caused by viral pathogens including influenza virus and other RNA viruses. Although NO and O(2)(-) have antimicrobial activity against bacteria, fungi, and parasites, in some viral infections they have an opposite effect. This exacerbation caused by NO and O(2)(-) is mediated by reactive nitrogen oxides, for example, peroxynitrite (ONOO(-)), generated by reaction of NO with O(2)(-). These nitrogen oxides have strong oxidation and nitration potential and can modify biological molecules, thereby creating oxidative and nitrative stress that contributes to pathogenic processes during viral infection. Nitrative stress-mediated 8-nitroguanosine formation during influenza or Sendai virus infection has been the focus of enormous interest because it involves unique biochemical and pharmacological properties such as redox activity and mutagenic potential. In this review, we discuss the nature and impact of nitrative stress in viral infection, with emphasis on nitrative stress-mediated viral pathogenesis, which we have recently been investigating.