RESUMO

Previous studies have demonstrated a diabetogenic effect of Venezuelan equine encephalitis (VEE) virus in hamsters. A preliminary study was conducted in which five 2- to 3-year-old rhesus monkeys were infected with the virulent Trinidad donkey strain of VEE virus and their carbohydrate metabolism was studied over 10 months. All animals developed mild clinical illness (rhinorrhea, cough, fever), were viremic, and developed antibodies. As compared with the results of preinoculation intravenous glucose tolerance tests (IVGTT), the monkeys had abnormally high glucose values by 2 months postinoculation (PI), progressively diminished insulin responses between 8 days and 5 months PI, and significantly lower glucagon curves 2, 5, and 10 months PI. Pancreatic histology and insulin content were normal. A second, controlled study was conducted of glucose and insulin metabolism in somewhat older (3- to 8-year-old) rhesus monkey after they were infected with both the Trinidad donkey strain of VEE virus and the attenuated VEE vaccine (TC-83). Groups of six monkeys received the virulent virus and the TC-83 vaccine, and five animals were sham-inoculated with saline. Monkeys inoculated with virulent virus became viremic, and 50% became febrile without overt signs of illness, whereas those given TC-83 virus remained afebrile and did not become viremic, but five of six developed antibodies. Intravenous glucose tolerance tests were performed and serum immunoreactive insulin responses to glucose administration measured before infection and 2 and 5 months later. No significant and consistent alterations of glucose or insulin responses were detected in the infected or control groups. Although several animals had preinoculation anti-islet cell antibodies, none developed new antibodies during the study.

Assuntos

Assuntos

RESUMO

Viral infections have been implicated in the induction of diabetes mellitus in man and laboratory animals. Since virus-specific immunofluorescence (FA) is detectable in hamster pancreas during the acute phase of Venezuelan encephalitis (VE), experiments were designed to correlate pathologic and virologic events with metabolic studies in VE-infected hamsters. Golden Syrian hamsters were inoculated s.c. in groups of four to 12 with 100,000 plaque-forming units (PFU) of the vaccine strain (TC-83) of VE or 1,000 PFU of the virulent Trinidad strain of VE. Ultrastructurally, during Trinidad infection, mature virions were associated with the cell surfaces and within pancreatic beta cells in contrast to absence of virus-related changes in TC-83-infected hamsters. Virus-specific-FA was noted in islet cells and acinar cells of Trinidad-infected hamsters. VE growth curves demonstrated viral replication in pancreas with both strains. Although ultrastructural and FA changes were much more prominent in Trinidad-infected hamsters in contrast to TC-83-infected hamsters during the first few days of illness, the rapid lethality of the Trinidad-infected group necessitated performing all metabolic studies in TC-83-strain-infected hamsters. Accordingly, for the metabolic studies, glucose tolerance tests (GTT) using 2 mg. or 5 gm./kg. glucose i.p. were performed in groups of hamsters acutely infected two days earlier with the TC-83 vaccine strain and in 24-day and 90-day convalescent hamsters after TC-83 vaccine strain. Samples were obtained for glucose and immunoreactive insulin (IRI) determinations. Glucose intolerance occurred in hamsters in each of the infected groups given 5 gm./kg. glucose except for the 90-day convalescent TC-83 group. Severely decreased IRI responses occurred in the 24-day and 90-day convalescent TC-83 hamsters following both 2- and 5-gm./kg. glucose. Pancreatic IRI content in 24-day convalescent TC-83 hamsters was within normal limits, suggesting a defect in IRI release from the beta cells at this stage of convalescence.

Assuntos