Immunity, Viral Pathology and Assessment of Immune Dysfunction in Virology and Toxicology

Abstract

General patterns of tissue injury are recognized as characteristic for certain groups of viruses and certain types of host/virus interactions. Acute viral infections, limited in time and space, tend to be accompanied by florid but brief virus replication cycles in tissues and lesions or signs of disease are largely attributable to the cytolytic effects of the virus on host cells. Chronic or persistent viral diseases tend to have low (or difficult to detect) levels of infectious virus on tissues and the lesions tend to be dominated by inflammation, antiviral immune responses and/or host tissue proliferation. At the cellular level, 3 general categories of response to viral infection are recognized: acute cellular swelling with eventual cytolysis, persistent infection, and transformation (neoplastic) infection. Acute cellular swelling may be accompanied by syncytial giant cell formation and/or viral inclusion bodies. Cells persistently infected with viruses though morphologically normal, are increasingly recognized as functionally deficient and may eventually display degenerative change. Transformation to neoplastic growth can be both benign or malignant in cellular expression. In vivo, the initial neutrophilic inflammatory response to virus-induced cellular necrosis is transient and is rapidly superseded by virus-specific inflammation mediated by both humoral and cellular factors and supplemented by the numerous inflammation amplification pathways. Vasculitis, a common but frequently unappreciated event, may produce nonspecific tissue damage via hemorrhage and ischemia in addition to providing a mechanism for egress of inflammatory factors into the areas of virus-induced cellular damage. During the healing phase, repair by substitution (e.g., fibrosis and scarring) or by proliferation of uninfected replacement cells may dominate sites of viral infection. Functional effects of viruses upon infected hosts are more common than is ordinarily appreciated and, in general, tend to involve control networks such as the nervous, endocrine and immune systems. In this regard, the similarities of mechanisms and effects of the actions of viruses and chemicals on lymphoid tissue are striking. The net systemic effects of these agents may well be enhanced susceptibility to infectious disease, altered responses to toxic agents, and greater sensitivity to chemically-mediated neoplastic transformation.