It is a great pleasure to contribute a few words of introduction to this Special Issue of MDPI’s Diseases entitled “Recent Studies of Arthropod-, Bat-, and Rodent-Borne Viruses: A Theme Issue in Honor of Professor Charles H [...]

There are few groups of viral zoonoses that have attracted such widespread publicity as the arenaviruses, particularly during the 1960’s and 1970’s when Lassa emerged as a major cause of haemorrhagic disease in West Africa. More than any other zoonoses, members of the family are used extensively for the study of virus-host relationships. Thus the study of this unique group of enveloped, single-stranded RNA viruses has been pursued for two quite separate reasons. First, lymphocytic choriomeningitis virus (LCM) has been used as a model of persistent virus infections for over half a century; its study has contributed, and continues to contribute, a number of cardinal concepts to our present understanding of immunology. LCM virus remains the prototype of the Arenaviridae and is a common infection of laboratory mice, rats and hamsters. Once thought rare in humans there is now increasing evidence of LCM virus being implicated in renal disease and as a complication in organ transplantation. Second, certain arenaviruses cause severe haemorrhagic diseases in man, notably Lassa fever in Africa, Argentine and Bolivian haemorrhagic fevers in South America, Guaranito infection in Venezuela and Chaparé virus in Bolivia. The latter is a prime example for the need of ever-continuing vigilance for the emergence of new viral diseases; over the past few years several new arenaviruses have been reported as implicated with severe human disease and indeed the number of new arenaviruses discovered since the last edition of this book have increased the size of this virus family significantly. In common with LCM, the natural reservoir of these infections is a limited number of rodent species (Howard, 1986). Although the initial isolates from South America were at first erroneously designated as newly defined arboviruses, there is no evidence to implicate arthropod transmission for any arenavirus. However, similar methods of isolation and the necessity of trapping small animals have meant that the majority of arenaviruses have been isolated by workers in the arbovirus field. A good example of this is Guaranito virus that emerged during investigation of a dengue virus outbreak in Venezuela (Salas et al. 1991). There is an interesting spectrum of pathological processes among these viruses. All the evidence so far available suggests that the morbidity of Lassa fever and South American haemorrhagic fevers due to arenavirus infection results from the direct cytopathic action of these agents. This is in sharp contrast to the immunopathological basis of ‘classic’ lymphocytic choriomeningitis disease seen in adult mice infected with LCM virus and the use of this system for elucidating the phenomenon of H2-restriction of the host cytotoxic T cell response (Zinkernagel and Doherty 1979). Despite the utility of this experimental model for dissecting the nature of the immune response to virus infection and the growing interest in arenaviruses of rodents, there remains much to be done to elucidate the pathogenesis of these infections in humans.

It is now accepted that as many as one-fifth of all human cancers may result from virus infection. Viral oncology owes much to the observations over 100 years ago that viruses may cause tumors in animals. Over 50 years later, detailed epidemiological and molecular studies have confirmed some retroviruses, hepadnaviruses, herpesviruses, and papillomaviruses as major causes of human cancers. The mechanisms of viral oncogenesis are complex, differing from virus to virus. As noted elsewhere, considerable advances have been made in developing vaccines against several viruses oncogenic for humans, notably some papilloma and hepatitis B viruses.

Emerging viral diseases now represent a major concern worldwide with the appearance of a new virus, or the re-emergence of a previously recognized virus with altered epidemiology and properties, occurring almost annually. Prominent examples in the last years include the sudden crossing of H5N1 avian influenza virus into humans in 1995, the unexpected West African outbreak of Ebola virus in 2014, the appearance of the Middle East respiratory syndrome related to the SARS virus first recognized in 2003, and the more recent epidemic of Zika virus in the Americas. These are just a few examples representing the constantly evolving relationship between pathogen and host, a process of evolution accelerated by population growth, climatic changes, and human activities.

Control and prevention of virus diseases require a comprehensive understanding of the epidemiology, the behavior of any vector, the availability of patient isolation where necessary, and effective use of vaccines where appropriate. Major achievements include the eradication of smallpox, the near eradication of poliomyelitis, and a major decline in many childhood diseases such as measles, mumps, rubella, and varicella. Education among those at risk is imperative, however, as is also an awareness of those who may deliberately disseminate viruses in order to further extreme political views.

The foundations of the science of medical virology are intertwined with the other life sciences, particularly microbiology and infectious diseases. Medical virology has a relatively brief history, spanning just over a century, but it is crowded with intriguing discoveries, stories of immense personal courage and numerous practical applications, many of which have had an overwhelmingly positive benefit on humankind. Its origins involved the replacement of centuries-old beliefs and theories with discoveries borne out of rigorous scientific investigation. Targeted prevention and control strategies could only be developed and implemented once the concept of the specificity of disease causation had been accepted, namely that infectious diseases are caused not by some common miasma (a mysteriously poisonous substance), but rather by specific agents. In a wider sense, the microbial sciences have played a pivotal role in the development of medical thought, particularly in applying scientific rigor in understanding pathological processes. Advances in understanding of infectious agents have led to improvements in human health and well-being that arguably have exceeded the contribution of any other branch of science. Indeed, many workers in this field have been awarded the Nobel Prize in Physiology or Medicine in recognition of their achievements.

Pathogenesis encompasses all the sequence of events accompanying acute and persistent infections. It includes entry of the virus into the body, multiplication and spread, the development of tissue damage, and the production of an immune response; the latter may contribute to the pathology of an infection. It includes the appearance of clinical signs and symptoms, the eventual resolution of the infection and, in most cases, virus elimination. Understanding viral disease pathogenesis requires knowledge of each of the stages of infection and an awareness of the underlying mechanisms. There may be variation from individual to individual in the severity and/or the duration of these events, but a sound working knowledge of a typical sequence associated with each infection is crucial in both making an accurate diagnosis and recommending the appropriate treatment.

Over the past 20 years, antiviral therapy has undergone a revolution and is now making a significant impact on the treatment of major virus diseases, for example HIV and viral hepatitis B and C. Targets include viral reverse transcriptases and proteases. The use of interferon to boost host immunity has also proved effective. Our understanding of chemotherapeutic strategies and drug resistance has become considerably more sophisticated since the widespread introduction of routine genome sequencing of virus isolates.