Colin R. Howard

Patterns of Infection

Viral infections can be classified as either transient or persistent , and within each of these categories an infection may be either localized (that is, confined to the epithelial surface where the virus initially enters), or systemic (that is, spreading more generally throughout body compartments, usually via the bloodstream). Under normal circumstances most common human infections typically lead to one of these four possible scenarios, transient local, systemic persistent infection, etc., depending on the virus. The outcome may be dependent upon age, variation among wild-type viruses, and whether or not the individual is immunosuppressed. Chronic infection caused by herpesviruses, viral hepatitis viruses B and C, and HIV represents the vast proportion of infections confronting the virologist.

Vaccines and Vaccination

Vaccination is one of the most effective intervention measures known to medical science. Apart from the eradication of smallpox and the near eradication of poliomyelitis, the incidence of major childhood diseases has declined dramatically in developed countries through the implementation of childhood immunization programs. However, effective vaccination protocols require a political will that is often lacking in many countries. Vaccines against diseases such as hepatitis B and certain papillomaviruses will make inroads into the prevalence of human cancer induced by these viruses. The introduction of vaccines against some viruses such as HIV, hepatitis C virus and others, has proved remarkably difficult, however, and a plethora of newer technologies have been investigated.

Adaptive Immune Responses to Infection

The adaptive immune response drives the destruction of infected cells and the neutralization of extracellular virus during the recovery process. In contrast to innate immunity adaptive immunity is antigen-specific, and takes at least several days to develop. Critical to the response is the cleavage of viral proteins into peptides that are then presented to the cells of the lymphoid system. An important component is the generation of immunological memory that permits a much more rapid response when the same virus is again encountered. A number of fundamental concepts in immunology have been revealed by the study of virus-infected cells.

Mechanisms of Viral Oncogenesis

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.

Hepatitis B and Hepatitis Delta Viruses

Hepatitis B is one of the world’s major unconquered diseases. Over 300 million people are chronic carriers of the virus, and a significant minority of these go on to develop cirrhosis or cancer of the liver from which over a million die each year. It is estimated that up to 2 billion people have been exposed to this virus at some time in their life. Reliable diagnostic procedures and vaccines have been available for several decades. Despite the availability of vaccines, however, there are still more than 600,000 deaths each year. Owing to the large number of chronically infected individuals, however, it will take several generations before such implementation has a significant impact on the incidence of chronic liver disease and related hepatocellular carcinoma. Antiviral therapy of hepatitis B is now having a significant impact on preventing patients progressing to chronic liver disease. Hepatitis delta virus is dependent upon the presence of hepatitis B virus and co-infection can lead to severe liver disease. Unique among all human viruses, the hepatitis delta viral genome acts as a satellite virus, with an RNA genome possessing many of the properties of ribozymes.

Control, Prevention, and Eradication

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.

Classification of Viruses and Phylogenetic Relationships

Abstract The taxonomy of viruses represents a unique classification system that recognizes boundaries among at first sight a continuum of properties. Genome sequencing has brought into sharp debate the origin of viruses, with RNA viruses perhaps having a separate evolutionary lineage. The criteria adopted for assessing the causal linkage between virus and disease deviates from those normally adopted for bacterial diseases and reflects those unique properties that underlie the principles of virus classification.

History and Impact of Virology

Abstract 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 of Virus Infections

Abstract 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.

Virion Structure and Composition

Abstract Extracellular virus consists of the viral genome surrounded by a protective coat of protein; the resulting nucleocapsid may be surrounded by an outer lipid envelope in which viral proteins are embedded. Viral proteins confer specificity as to the range and type of host cell that may be infected. The assembly of spherical particles follows the principles of cubic symmetry with individual asymmetrical proteins clustered into symmetrical structures grouped around the cubic axis of symmetry to form an icosahedron. X-ray diffraction studies have revealed how viral proteins expose ligands important for the recognition of host cell receptors and the properties of antigenic variants. The properties of viral proteins determine temperature sensitivity and resistance to environment and chemical factors.