Principles of Virology, Volume 1. Jane Flint
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Courtesy of Dr. Pamela Hullinger, California Department of Food and Agriculture.
Viruses Can Cause Human Disease
With such constant exposure, it is nothing short of amazing that the vast majority of viruses that infect us have little or no impact on our health or well-being. As described in Volume II, we owe such relative safety to our elaborate immune defense systems, which have evolved under the selective pressure imposed by microbial infection. When these defenses are compromised, even the most common infection can be lethal. Despite such defenses, some of the most devastating human diseases have been or still are caused by viruses; these diseases include smallpox, yellow fever, poliomyelitis, influenza, measles, and AIDS. Viral infections can lead to life-threatening diseases that impact virtually all organs, including the lungs, liver, central nervous system, and intestines. Viruses are responsible for approximately 15% of the human cancer burden, and viral infections of the respiratory and gastrointestinal tracts kill millions of children in the developing world each year. As summarized in Volume II, Appendix, there is no question about the biomedical importance of these agents.
Viruses Can Be Beneficial
Despite the appalling statistics from human and agricultural epidemics, it is important to realize that viruses can also be beneficial. Such benefit can be seen most clearly in the marine ecosystem, where virus particles are the most abundant biological entities (Box 1.1). Indeed, they comprise 94% of all nucleic acid-containing particles in the oceans and are 15 times more abundant than Bacteria and Archaea. Viral infections in the ocean kill 20 to 40% of marine microbes daily, converting these living organisms into particulate matter. In so doing they release essential nutrients that supply phytoplankton at the bottom of the ocean’s food chain, as well as carbon dioxide and other gases that affect the climate of the earth. Pathogens can also influence one another: infection by one virus can have an ameliorating effect on the pathogenesis of a second virus or even bacteria. For example, mice latently infected with some murine herpesviruses are resistant to infection with the bacterial pathogens Listeria monocytogenes and Yersinia pestis. The idea that viruses are solely agents of disease is giving way to an appreciation of their positive, even necessary, effects, and a realization that their unique properties can actually be harnessed for human benefit (Volume II, Chapter 9).
Viruses “R” Us
Every cell in our body contains viral DNA. Human endogenous retroviruses, and elements thereof, make up about 8% of our genome. Most are inactive, fossil remnants from infections of germ cells that occurred over millions of years during our evolution. Some of them are suspected to be associated with specific diseases, but the regulatory sequences and protein products of other endogenous retroviruses have been coopted during our evolution for their unique functions. For example, retroviral gene products may play a role in the regulation of pluripotency in germ cells, in transmission of signals at neuronal synapses, and clearly in the way that we give birth. The development of the human placenta depends on cell fusion promoted by a retroviral protein. If not for these endogenous retroviruses, we might be producing our young in eggs, like birds and reptiles.
Recent genomic studies have revealed that our viral “heritage” is not limited to retroviruses. Human and other vertebrate genomes harbor sequences derived from several other RNA and DNA viruses. As many of these insertions are estimated to have occurred some 40 million to 90 million years ago, this knowledge has provided unique insight into the ages and evolution of their currently circulating relatives. The conservation of some of these viral sequences in vertebrate genomes suggests that they may have been selected for beneficial properties over evolutionary time.
Viruses Can Cross Species Boundaries
Although viruses generally have a limited host range, they can and do spread across species barriers. As the world’s human population continues to expand and impinge on the wilderness, cross-species (zoonotic) infections of humans are occurring with increasing frequency. In addition to the AIDS pandemic, the highly fatal Ebola hemorrhagic fever, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS) are recent examples of viral diseases to emerge from zoonotic infections. The influenza virus H5N1 continues to spread among poultry and wild birds in areas of the Middle East and Asia. The virus is deadly to humans who catch it from infected birds. The frightening possibility that it could gain the ability to spread among humans is a major incentive for monitoring for person-to-person transmission in case of infection by this and other pathogenic avian influenza viruses. Given the eons over which viruses have had the opportunity to interact with various species, today’s “natural” host may simply be a way station in viral evolution.
Viruses Are Unique Tools To Study Biology
Because viruses are dependent on their hosts for propagation, studies that focus on viral reprogramming of cellular mechanisms have provided unique insights into genetics, cellular biology, and functioning of host defenses. Groundbreaking studies of viruses that infect bacteria (called bacteriophages) in the mid-20th century established the molecular basis of genetic inheritance. Through development and use of stringent, quantitative methods with these relatively simple biological entities, this research confirmed that DNA encodes genes and genes encode proteins. General mechanisms of genetic recombination, repair, and control of gene expression were also elucidated, laying the foundations of modern molecular biology and recombinant DNA technology. Subsequent studies of animal viruses established many fundamental principles of cellular function, including the presence of intervening sequences in eukaryotic genes. The study of cancer (transforming) viruses established the genetic basis of this disease.
With the development of recombinant DNA technology and our increased understanding of viral systems, it has become possible to use viral genomes as vehicles for the delivery of genes to cells and organisms for both scientific and therapeutic purposes. The use of viral vectors to introduce genes into various cells and organisms to study their function has become a standard method in biology. Viral vectors are also being used to treat human disease, for example, via “gene therapy,” in which functional genes delivered by viral vectors compensate for faulty genes in the host cells (Volume II, Chapter 9).
The study of viruses has contributed in a unique way to the field of anthropology. As ancient humans moved from one geographic area to another, the viral strains unique to their original locations came along with them. The presence of such strains can be detected by analysis of viral nucleic acids, proteins, and antibodies from ancient human specimens and in modern populations. Together with archeological information, identification of these virological markers has been used to trace the pathways by which humans came to inhabit various regions of our planet (Fig. 1.2).
Figure 1.2 Tracking ancient human migrations by the viruses they carried. The polyomavirus known as JC virus is transmitted among families and populations and has coevolved with humans since the time of their origin in Africa. This virus produces no disease in normal, healthy people. Most individuals are infected in childhood, after which the virus establishes a persistent infection in the gastrointestinal tract and is shed in urine. Analysis of the genomes of JC virus in human populations from different geographic locations has suggested an expansion of ancient humans from Africa via two distinct migrations, each carrying a different lineage of the virus. Results from these studies are consistent with analyses of human DNAs (shown by the solid line). They also suggest an additional route that was undetectable in the human DNA analyses (indicated by the dashed line). Data from Pavesi A. 2005. J Gen Virol 86:1315–1326.
Virus