8 Pathogenesis of Retrovirus-induced Disease

Abstract

I. INTRODUCTION
Retroviral infections manifest a variety of pathological syndromes. The very nature of provirus integration and persistence emphasizes the close interrelationship between virus and host that often, but by no means always, results in disease. Although neoplasia has always been foremost in investigations of pathogenesis, retroviruses also elicit several kinds of nonmalignant diseases that represent significant causes of morbidity and mortality in infected host populations.

The diseases most commonly associated with retroviruses can be divided into four groups: (1) malignant tumors; (2) proliferative diseases that, although not necessarily neoplastic, may nonetheless be fatal; (3) anemias; and (4) slow, sporadic or chronic, degenerative diseases sometimes resembling “autoimmune” disease, affecting hematopoietic, neural, and other tissues. Tumors can be further classified on the basis of the tissue or origin: (1) sarcomas, which arise from connective (mesenchymal) tissue (e.g., fibroblasts, muscle cells, and chondrocytes); (2) carcinomas, which arise from epithelial tissues (e.g., epithelia of mammary glands); and (3) leukemias and lymphomas, which involve cells of the hematopoietic system. The majority of retrovirus-induced tumors fall into this third category, and therefore one section of this chapter is devoted to a general description of the hematopoietic lineages, using the mouse as a model system. Now that the molecular genetics of retroviruses is well established, it has become increasingly important to understand the underlying cellular mechanisms involved in normal differentiation in order to elucidate the alterations that occur during the pathogenic process or neoplastic conversion. Such studies can be undertaken at two levels: the target cell...