For over three decades, the electron microscope has been an integral part of the research program of the Epidemiology Section regarding the etiologic role, natural history and physical characteristics of various important enteric viruses. Past highlights of these investigations have included inquiry into the etiology of diseases of unknown cause involving studies of fastidious agents of disease that defied cultivation in any cell culture system. The electron microscope played a major role (i) in the discovery of the 27nm Norwalk virus (now known as a member of the norovirus genus in the calicivirus family) and the establishment of its etiologic role in human diarrheal disease, and (ii) in collaboration with the Hepatitis Viruses Section, in the discovery of the 27nm hepatitis A virus particle and establishment of its etiologic role in infectious hepatitis. It also was used as an important epidemiologic tool for the detection of rotaviruses in stools of infants and young children hospitalized with diarrhea and helped in establishing the importance of these agents in severe diarrhea of infants and young children. Although intensive efforts have been made, the Norwalk and related human enteric noroviruses have yet to be cultivated in any tissue culture system. This, along with the expression of 27nm virus-like particles of certain members of this group of agents have contributed to the continuing important role of the electron microscope in the research program of the Epidemiology Section. The electron microscope has been used predominantly by Kim Green for the norovirus unit as the human noroviruses cannot be grown in cell culture.The electron microscope has continued to be an important primary and adjunctive tool in various capacities. For example,it was used in various studies including examination of (1) stools obtained from a chimpanzee that had developed clinical manifestations consistent with Kawasaki disease after inoculation with human Kawasaki disease material. We looked for viral agents by direct EM and in one stool by IEM also (in collaboration with Dr. Purcell);(2) Norwalk VLPs composed of VP1 and VP2 to be used in a chimpanzee inoculation study; (3) San Miguel Sea Lion Virus (SMSV) VLPs from yeast and baculovirus expression (prepared at Florida State Univ); (4) recombinant baculovirus expressing GII4 capsid protein from norovirus strain HS 191 for VLPs (from Ohio Agricultural Research and Development Center); (5) cell culture fluid and pellet following inoculation with Hom-1 (SMSV); (6) purification procedure for norovirus strain St. Cloud VLPs; (7) a new mink calicivirus virion preparation; (8) RRV grown in cell culture; (9) rotavirus VLPs; and (10) hexavalent rotavirus vaccine from India.
