Michael B. A. Oldstone Knihy

In Viruses, Plagues, and History, virologist Michael Oldstone explains the scientific principles of viruses and epidemics while relating the past and present history of the major and recurring viral threats to human health, and how they have influenced human events.

Reoviruses are one of the most important viral groups for understanding the molecular and genetic basis for viral pathogenesis. These two volumes cover virtually all aspects of reovirus biology. Volume I begins with a review of reovirus structure; further chapters deal with functions of the reovirus structural proteins, the assembly of the genome, and reovirus mutants. Volume II reviews general mechanisms of reovirus persistent infection and cytopathic effects, and then discusses reovirus-induced disease in specific organ systems including the heart, nervous and endocrine systems, liver and biliary system, and intestine. Together, these two volumes provide a current and comprehensive review of the mammalian reoviruses.

The conceptual basis for molecular mimicry was first defined in the early 1980s when monoclonal antibodies against viruses were also shown to react with non-viral host protein; in this case, measles virus phosphoprotein cross-reacted with host cell cytokeratin, herpes simplex virus type 1 with host-cell vimentin and vaccinia virus with host-cell intermediate filaments. Following this discovery, others emerged, again at the clonal level, that T cell clones against proteins from a variety of infectious agents also reacted with host antigenic determinants. The clonal distinction was imperative for the initial definition of mimicry. At least 30 years prior to our initial description of molecular mimicry involving cross-reactions between numerous microbes, on the polyclonal antibody level, streptococcus was believed to react with renal glomeruli, heart and basal ganglia to account for the glomerulonephritis, heart and valvular disease and chorea, respectively. However, subsequent research showed that the nephritis was caused by immune complex deposits and the tissue damage they produced. Later, in 1990, the cross-reactivity of streptococcal antigen with myocardial antigens on a clonal level was uncovered. Hence, for both historical reasons and mechanistic understanding, it is best to provide evidence for cross-reactivity at the clonal level to prove that molecular mimicry exists.

The National Institute of Mental Health (NIMH) AIDS Program is the fourth largest acquired immune deficiency syndrome (AIDS) program within the National Institutes of Health (NIH). Since 1983, our program's contributions have concentrated on two major areas. The first has been to develop effective strategies to prevent or reduce behaviors that place individuals at risk for human immunodeficiency virus type 1 (HIV-1) infection. The second has been to support and foster research to enhance our understanding of the profound impact of H IV-1 infection on the central nervous system (eNS). The brain appears to be a prime target of the virus and may serve as a reservoir for the virus. Post mortem examination of brain tissue has provided evidence of eNS cell damage in 80%-90% of people who die with AIDS. For about 10%-20% of people with AI DS, mild neuropsychological symptoms are the first signs of the disease. Approximately 20% of individuals infected with HIV-1 develop AIDS dementia complex. The symptoms include apathy, difficulty concentrat ing, irritability, depression, and personality changes. In the later stages of the disease, people may experience psychiatric disor ders. Death usually occurs within 6 months of the appearance of those more severe symptoms. Up to 90% of children infected with H IV-1 experience attention and concentration difficulties and often experience neurodevelopmental delay or regression over time.