Conclusion

Study of the pathogenesis of retroviruses has already led to a large amount of useful information. A wide variety of pathogenic mechanisms have been uncovered, highlighting the diverse impact that retroviruses can have on their hosts. Despite this progress, a complete picture of the pathogenesis of even one of these infections is still lacking. Some pathogenic strains cannot be grown in vitro, making analyses of these agents extremely difficult. The factors that control the types of cells that are infected and altered by the viruses remain mysterious. The ways in which each of the viral genes and control elements act together to induce disease is only partly understood for some retroviruses. Although the molecular mechanisms controlling retroviral replication are now quite clear, the critical contribution of viral replication and viral load to pathogenesis has been appreciated only recently. Some virus-encoded proteins perform specialized functions that are essential for disease induction. The recent discovery that MMTV encodes a superantigen has revealed an additional and novel way in which one retrovirus establishes infection by exploiting the host immune system. Other retroviruses almost certainly manipulate the immune response to their advantage by mechanisms that remain poorly understood. Host genes have an important role in modulating the outcome of infection. However, only a few of these genes have been identified, and the ways in which these genes affect pathogenesis remain obscure in most cases.

Studies of retrovirus-induced oncogenesis should continue to make major contributions to our understanding of the molecular mechanisms by which cell growth and differentiation are altered during transformation. In addition, pathways that are important in normal cells continue to be illuminated by studies of temperature-sensitive retroviruses that transform differentiating hematopoietic cells. Even though a large number of genes involved in oncogenesis and differentiation have already been identified, it seems likely that additional genes await discovery. The ability to use retroviruses in combination with genetically engineered animals has expanded the tools available for studies of oncogene cooperativity. Recent advances in our understanding of the mechanisms by which cell cycling and survival are controlled are only beginning to be incorporated into hypotheses about the ways in which retroviruses stimulate cell growth.

Much remains to be learned concerning the transmission and epidemiology of retroviruses. Advances in these areas are critical to controlling the spread of HIV, HTLV, and other naturally occurring infections. Studies addressing the evolutionary relationships among many of these agents may provide insights into the mechanisms by which “new” viruses emerge and spread through large populations. All of these aspects of retroviral pathogenesis present major challenges for future research and are important if disease induction is to be understood and controlled.