Inhibition of rotaviruses by selected antiviral substances: mechanisms of viral inhibition and in vivo activity.

Several RNA virus inhibitors were evaluated against simian (SA11) rotavirus infections in vitro and murine rotavirus gastroenteritis in vivo. Test compounds included 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin), 3-deazaguanine (3-DG), 3-deazauridine, and 9-(S)-(2,3-dihydroxypropyl)adenine [(S)-DHPA]. All drugs inhibited total infectious SA11 virus yields in MA-104 cells.

Inhibition of bluetongue and Colorado tick fever orbiviruses by selected antiviral substances.

The effects of four ribonucleic acid virus inhibitors were evaluated in cell cultures and in mice to determine inhibitory effects against bluetongue virus and Colorado tick fever virus (CTFV). Test compounds included 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin), 3-deazaguanine, 3-deazauridine, and 9-(S)-(2,3-dihydroxypropyl)adenine. Ribavirin-2',3',5'-triacetate (ribavirin triacetate) was evaluated in vivo against CTFV.

Trypsin enhancement of rotavirus infectivity: mechanism of enhancement.

The infectivity of most rotaviruses is enhanced by treatment with trypsin. We studied the mechanism of enhancement of examining the effect of trypsin on rotavirus infectivity, aggregation, early interactions with host cells, and structure. The results indicated that trypsin does not increase levels of infectious virus by dispersion of aggregates or affect the efficiency or rate of attachment of virus to cells.

Effects of diazepam on body temperature of the aged squirrel monkey.

Hypothermia was produced by IM administration of diazepam (0.125-0.5 mg/kg) to squirrel monkeys of various ages (2-16 years) in a thermoneutral (23 +/- 0.

Hypothermia produced in aged squirrel monkeys by central administration of taurine.

Accidental hypothermia and heatstroke are more common in aged populations. While peripheral factors are undoubtedly important to the high incidence of dysthermia in the aged, alterations in central temperature controls associated with aging may be primarily responsible. It has been shown that the sensitivity of the hypothalamus to neurotransmitters is changed in aged animals, and it may be that similar alterations in central temperature controls underlie the increased susceptibility to dysthermia.

Role of two particle types in bovine rotavirus morphogenesis.

The involvement of light (L) and dense (D) bovine rotavirus particle types during virus replication has been studied. It was found that infectious parental L virions are uncoated in vivo to a particle similar to native D particles. Differences in the rate of synthesis and relative yields of L and D particles in MDBK and MA-104 cells have been detected.

Reduced febrile responses to peripheral and central administration of pyrogen in aged squirrel monkeys.

There is long-standing controversy as to whether fever capacity is reduced in aged man. Although loss of this cardinal sign of disease would be an impediment to diagnosis and treatment, there has been no previous research on altered febrile responses using aged primate models. In the present experiments the febrile reaction to IV Salmonella typhosa endotoxin was reduced in monkeys over 14 years old and in one-third of those 10-14 years of age compared with that of younger animals.

Production of high-titer bovine rotavirus with trypsin.

Titers of bovine rotavirus in excess of 10(9) immunofluorescent infectious units per ml of culture fluids have been produced, using trypsin treatment of the virus. Infectivity of preparations of the virus can be increased with as little as 1 ng of trypsin per ml, with maximum increases of 1 to 2 log10 with 1 microgram of trypsin per ml. The virus grows to titers in excess of 10(5) immunofluorescent units per ml in MDBK, LLC-MK2, MA-104, and HeLa cells.