The electron microscope has been a mainstay in the study of gastroenteritis viruses. Two major groups of gastroenteritis viruses--the 27nm Norwalk virus and the 70nm human rotaviruses-were discovered at NIH and in Australia, respectively, (as well as the hepatitis A virus at NIH, in collaboration with the Hepatitis Section) with the use of the electron microscope. It is remarkable that in this era of tissue culture virology, these agents were discovered initially without the use of an in vitro tissue culture system, since they could not be grown directly from clinical specimens in cell culture. We have applied the term, """"""""direct virology,"""""""" to this method of examining viruses from clinical specimens by electron microscopy. Although second and third generation tests have been developed for the detection of the Norwalk group of viruses and the rotaviruses, the electron microscope is still an indispensable tool for the study of these gastroenteritis viruses. It is also the most rapid diagnostic tool for detection of rotavirus from a clinical specimen and is the only method available for diagnosing infection with certain 27nm viruses associated with epidemic nonbacterial gastroenteritis. It also is important for: (1) providing direct visualization of virus particles from density gradients (to establish their morphologic appearance, e.g., single or double capsid, integrity of capsid structure, and to determine presence or absence of particles or their quantitation); (ii) providing direct visualization of particles from clinical specimens to determine their identity, if feasible; (iii) attempting to visualize the site of activity of antibodies such as monoclonal antibodies or recombinant virus induced antibodies; and (iv) serologic studies performed by immune electron microscopy to determine the antigenic relationships of fastidious gastroenteritis agents that cannot be propagated in cell culture such as the human group C rotaviruses, and the Norwalk group of agents. However, its most important and creative role is in its application to the detection of new, heretofore unknown, agents of acute infectious gastroenteritis and other diseases as well.
