Reactive oxygen species and nitric oxide in viral diseases

Metabolites derived from superoxide (o2 •−) and nitric oxide (NO•) play an important role in antimicrobial and antitumoral defense, but may also harm the host. Low levels of such metabolites can also facilitate viral replication because of their mitogenic effects on cells. Most viruses grow better in proliferating cells, and indeed, many viruses induced in their host cell changes similar to those seen early after treatment with mitogenic lectins. Influenza and paramyxoviruses activate in phagocytes the generation of superoxide by a mechanism involving the interaction between the viral surface glycoproteins and the phagocyte's plasma membrane. Interestingly, viruses that activate this host defense mechanism are toxic when injected in the bloodstream of animals. Mice infected with influenza virus undergo oxidative stress. In addition, a wide array of cytokines are formed in the lung, contributing to the systemic effects of influenza. Oxidative stress is seen also in chronic viral infections, such as AIDS and viral hepatitis. Oxidant production in viral hepatitis may contribute to the emergence of hepatocellular carcinoma, a tumor seen in patients after years of chronic inflammation of the liver. Antioxidants and agents that downregulate proinflammatory cytokines and lipid mediators may be a useful complement to specific antiviral drugs in the therapy of viral disease

Differential Regulation of Inducible Nitric Oxide Synthase Production in Bovine and Caprine Macrophages

Inducible nitric oxide synthase (iNOS) regulation in human and murine macrophages in vitro differs considerably. In this study, expression of macrophage iNOS in ruminants was addressed. Nitric oxide (NO) output by cattle and goat macrophages was as different as that by human and mouse macrophages. Bovine macrophages activated by heated Salmonella dublin or lipopolysaccharide (LPS) expressed high levels of iNOS mRNA, protein, and enzyme activity. Analogously cultured caprine macrophages did not respond to these and other activators by NO generation and iNOS expression. The lack of response was not due to general unresponsiveness to stimuli. Caprine iNOS mRNA was induced by stimulation of caprine macrophages with LPS, as shown by reverse transcription polymerase chain reaction. The level of mRNA expression in activated goat macrophages was lower than in resting bovine macrophages. A caprine 372-bp iNOS mRNA fragment that was sequenced closely resembled the bovine counterpart. This points to species-specific iNOS gene regulation

Differential Regulation of Inducible Nitric Oxide Synthase Production in Bovine and Caprine Macrophages

Inducible nitric oxide synthase (iNOS) regulation in human and murine macrophages in vitro differs considerably. In this study, expression of macrophage iNOS in ruminants was addressed. Nitric oxide (NO) output by cattle and goat macrophages was as different as that by human and mouse macrophages. Bovine macrophages activated by heated Salmonella dublin or lipopolysaccharide (LPS) expressed high levels of iNOS mRNA, protein, and enzyme activity. Analogously cultured caprine macrophages did not respond to these and other activators by NO generation and iNOS expression. The lack of response was not due to general unresponsiveness to stimuli. Caprine iNOS mRNA was induced by stimulation of caprine macrophages with LPS, as shown by reverse transcription polymerase chain reaction. The level of mRNA expression in activated goat macrophages was lower than in resting bovine macrophages. A caprine 372-bp iNOS mRNA fragment that was sequenced closely resembled the bovine counterpart. This points to species-specific iNOS gene regulatio

Cytopathic bovine viral diarrhea viruses (BVDV): emerging pestiviruses doomed to extinction

Bovine viral diarrhea virus (BVDV), a Flaviviridae pestivirus, is arguably one of the most widespread cattle pathogens worldwide. Each of its two genotypes has two biotypes, non-cytopathic (ncp) and cytopathic (cp). Only the ncp biotype of BVDV may establish persistent infection in the fetus when infecting a dam early in gestation, a time point which predates maturity of the adaptive immune system. Such fetuses may develop and be born healthy but remain infected for life. Due to this early initiation of fetal infection and to the expression of interferon antagonistic proteins, persistently infected (PI) animals remain immunotolerant to the infecting viral strain. Although only accounting for some 1% of all animals in regions where BVDV is endemic, PI animals ensure the viral persistence in the host population. These animals may, however, develop the fatal mucosal disease, which is characterized by widespread lesions in the gastrointestinal tract. Cp BVD virus, in addition to the persisting ncp biotype, can be isolated from such animals. The cp viruses are characterized by unrestrained genome replication, and their emergence from the persisting ncp ones is due to mutations that are unique in each virus analyzed. They include recombinations with host cell mRNA, gene translocations and duplications, and point mutations. Cytopathic BVD viruses fail to establish chains of infection and are unable to cause persistent infection. Hence, these viruses illustrate a case of “viral emergence to extinction” – irrelevant for BVDV evolution, but fatal for the PI host

Pestiviruses.

Pestiviruses cause economically important diseases among domestic ruminants and pigs, but they may also infect a wide spectrum of wild species of even-toed ungulates (Artiodactyla). Bovine viral diarrhea virus (BVDV) and Border disease virus of sheep infect their hosts either transiently or persistently. Cellular and humoral immunotolerance to the infecting strain is a unique feature of persistent infection (PI) by ruminant pestiviruses. Persistence, caused by transplacental infection early in fetal development, depends on virally encoded interferon antagonists that inactivate the host's innate immune response to the virus without globally interfering with its function against other viruses. At epidemiological equilibrium, approximately 1-2% of animals are PI. Successful BVDV control programs show that removal of PI animals results in viral extinction in the host population. The nucleotide sequences of ruminant pestiviruses change little during persistent infection. Nevertheless, they display large heterogeneity, pointing to a long history of virus-host coevolution in which avirulent strains are more successful

Bovine viral diarrhoea: a playground for virologists and a target for eradication.

197 adverse reactions of Swissmedic-authorized veterinary medicinal products were reported during the year 2012 (2011: 167). Species and drug classes remain unchanged over the years: most of the reports related to reactions following the use of antiparasitic products (37.6 %), antiinfectives (15.7 %) or non-steroidal antiinflammatory drugs (11.7 %) in companion animals (94 dogs and 53 cats) followed by cattle/calves (29). Additionally, 45 cases transmitted by the Swiss Toxicological Information Centre in Zürich were processed. We discuss a paradoxical reaction under the potential influence of acepromazine as well as a modified protocol for treating permethrin intoxication in cats. Finally, the vaccinovigilance program received 95 declarations following the application of various vaccines, mainly to dogs or cats