The enteroviruses: recent advances.

New information accrues periodically in the ledger accounting for infections and diseases associated with the human enteroviruses. The discoveries of "new" serotypes and how they affect people are subjects of continuing attention. Some other relevant information on "old" serotypes relates to variations in age-specific attack rates and associated morbidity and mortality for neonates and older infants. Among the morbidity reports are recounts during outbreaks of virus-positive cerebrospinal fluids (CSFs) that initially may not have cytological or biochemical abnormalities. Prolonged enterovirus infections may develop in persons having agammaglobulinemia. Lastly, some provocative associations concern the pathologic expressions of enteroviruses in the development and persistence of injury to the heart (myocardiopathies) and the pancreas (insulin-dependent diabetes mellitus).

A mixed epidemic associated with echovirus types 6 and 11: virologic, clinical and epidemiologic studies.

During 1979, an outbreak of mixed enterovirus infections occurred in Kansas City and adjacent communities. Sixty-six enteroviruses and 7 adenoviruses were recovered from 73 persons in a survey hospital population. Twenty-eight persons yielded echovirus type 11, 22, echovirus type 6, and 16 either echovirus type 9 or Coxsackieviruses group B, types 2 and 3. This study describes some of the clinical, virologic and epidemiologic characteristics of the outbreak. A major finding relates to the recovery of enteroviruses from cerebrospinal fluids with essentially normal leukocyte counts.

Clinical and pathogenetic studies of Medical Lake macaque virus infections in cynomolgus monkeys (simian varicella).

The Medical Lake macaque (MLM) virus produced varicelliform eruptions in cynomolgus monkeys. Not all experimentally infected monkeys developed overt disease; viremia was found, and specific antibodies were detected. Specific lesions were found in skin, lymph nodes, and spleen. Focal inflammatory lesions were present in liver, pancreas, and lung (after intratracheal instillation of virus). MLM virus was recovered from these and other organs. The temporal movements of MLM virus in and out of primary and secondary target organs remained partially unsolved. MLM virus is related to the Wu strain of varicella virus.

The pathogenesis of simian varicella virus in cynomolgus monkeys.

The MLM herpesvirus is infectious for cynomolgus monkeys. The disease in this species, possibly modulated by preinoculation antibody resembles human varicella. Virus has been recovered from blood during the early incubation period, and from liver, lymph nodes, kidney, bladder and urine during the eruptive period of infection. The major target organs were skin and liver; specific pathological changes developed in both. Appropriate antibody responses, including those to Herpesvirus varicellae followed infections mounted by parenteral inoculation of cynomolgus monkeys.

Human and primate poxviruses: I. Growth characteristics of cytolytic and tumor variants.

The dual potential of poxviruses to be cytolytic and tumorgenic has been extended. Yaba monkey tumor virus formed foci on monkey and human embryonic cells. Cytolytic or plaque-forming virus was isolated from Yaba tumor homogenates by selective sucrose centrifugation and passage through monkey or human embryonic cells. Monkey pox virus (MPV) was cytolytic for monkey cells or human embryonic cells, but upon passage onto young monolayers of human carcinoma cells, HeLa, produced a restricted cytopathic effect on first transfer, foci on second transfer and cytolysis after the fourth transfer. If HeLa monolayers were compact, the rapid growth precluded overt expression of cytolytic MPV. Electron micrographs of cytolytic Yaba indicated that Yaba development was similar to vaccinia and MPV but not totally organized. Growth curves of vaccinia, MPV and cytolytic Yaba were essentially identical in monkey and human embryonic cell lines.

Evaluation of enterovirus immune horse serum pools for identification of virus field strains.

Immune horse sera to 42 enterovirus immunotypes were pooled according to the Lim Benyesh-Melnick and the "intersecting serum" schemes. Each serum was diluted in the pools to contain 50 antibody units. After it was established that the pools correctly neutralized prototype virus strains, they were evaluated in tests against 273 enterovirus field strains representing most of the viral types included in the pools. With test virus doses of 10-100 TCD(50), most of the poliovirus and coxsackievirus field strains were correctly identified in both schemes, but a number of the echoviruses were neutralized by heterotypic pools, particularly in the Lim Benyesh-Melnick scheme. However, at higher test virus doses of 320-3200 TCD(50), little heterotypic neutralization occurred in either scheme, and 93-94% of the virus field strains were correctly identified in each scheme. With these larger virus doses, breakthrough tended to occur in homologous pools by the 7th day, but rarely by the 5th day. Since the Lim Benyesh-Melnick pool scheme employs 8 pools as compared with 13 for the intersecting serum scheme, and since the two schemes were equally satisfactory for identifying virus field strains at test virus doses of 320-3200 TCD(50), immune horse sera will be pooled by the former scheme, thus utilizing fewer pools, for distribution to qualified viral diagnostic laboratories.

Viremia and virus measurements of rabbit pox in CV-1 cells.

Rabbit pox virus (RPV) produced cytopathic effect (CPE) in five types of cells grown in tissue cultures. The CPE on CV-1 cells was characterized by cell fusion and lysis. The CV-1 line is a useful and sensitive cell culture for measuring concentrations of RPV in blood and tissues of infected rabbits. Viremia was detected between the 2nd and 4th days after parenteral infection. By the 6th and 7th days, the concentration of RPV in various tissues ranged from 10(5-3) to 10(8-5) TCID(50)/g. Cross-reactivity was demonstrated by the fluorescent-antibody technique between rabbit pox, vaccinia, and monkey pox viruses.