Animal models of human immunodeficiency virus infection. Public Health Service Animal Models Committee.

The search for a model of HIV infection continues. While much of the initial work focussed on animal models of AIDS, more recent efforts have sought animal models of HIV infection in which one or more signs of AIDS may be reproduced. Most initial small animal modelling efforts were negative and many such efforts remain unpublished.

Protective and toxic effects of a nuclease-resistant derivative of polyriboinosinic-polyribocytidylic acid on Venezuelan equine encephalomyelitis virus in rhesus monkeys.

Polyriboinosinic-polyribocytidylic acid, stabilized with poly-L-lysine and carboxymethylcellulose (poly ICLC), favorably alters the pathogenesis of Venezuelan equine encephalomyelitis virus infection in rhesus monkeys by decreasing the number of infected monkey that become detectably viremic and by delaying the onset of viremia in the remaining monkeys. Poly ICLC is known to induce high circulating levels of interferon in primates, and the interferon system is assumed to be the mechanism by which poly ICLC exerts its antiviral effect. Poly ICLC treatment was associated with a few deaths, but only under certain conditions of infection and handling.

Studies of the coagulation system and blood pressure during experimental Bolivian hemorrhagic fever in rhesus monkeys.

Experimental infection of rhesus monkeys (Macaca mulatta) with Machupo virus produced a hemorrhagic disease similar to that of Bolivian hemorrhagic fever in humans. The disease in infected animals was also characterized by the development of hypotension and coagulation abnormalities as indicated by severe thrombocytopenia and prolongation of the activated partial thromboplastin time. Evidence for disseminated intravascular coagulation was inconclusive due to the presence of normal to elevated fibrinogen levels, relatively low levels of circulating fibrin split products, and the lack of widespread fibrin thrombus deposition.

Effect of a nuclease-resistant derivative of polyriboinosinic-polyribocytidylic acid complex on yellow fever in rhesus monkeys (Macaca mulatta).

Rhesus monkeys (Macaca mulatta) treated with a newly developed nuclease-resistant complex of polyriboinosinic-polyribocytidylic acid, poly-L-lysine, and carboxymethylcellulose [poly (ICLC)] did not die after challenge with virulent Asibi strain yellow fever (YF) virus. The strain of virus is sensitive to the effects of interferon in vitro and is lethal for rhesus monkeys four to six days after subcutaneous administration of 1,000 plaque-forming units of the virus. The mortality rate was reduced in monkeys initially treated 8 hr before or after inoculation of virus but was unchanged in monkeys initially treated 24 hr after challenge.

Inactivated Venezuelan equine encephalomyelitis virus vaccine complexed with specific antibody: enhanced primary immune response and altered pattern of antibody class elicited.

Complexes of formalinized Venezuelan equine encephalomyelitis (VEE) virus vaccine and specific IgG formed at antigen-antibody equivalence enhanced the immune responses of rhesus monkeys (Macaca mulatta). The predomonant class of antibody elicited by complexes was IgG. In contrast, lower titers of antibody and a more biphasic (IgG-IgM) response were observed after exposure of monkeys to the vaccine alone.

Small-particle aerosols of antiviral compounds in treatment of type A influenza pneumonia in mice.

Three chemotherapeutic drugs active against type A influenza virus (amantadine, rimantadine, and ribavirin) were tested as therapeutic agents against established infections with influenza virus in mice. The drugs were administered intraperitoneally or as aerosols either from 6 hr to four days or from three to seven days after infection. Small-particle aerosols were administered continuously 24 hr per day.

Changes in blood serum constituents and hematologic values in Macaca mulatta with Rocky Mountain spotted fever.

Forty-seven male Macaca mulatta, 3 to 4 kg weight, were inoculated intravenously or subcutaneously with various doses of yolk sac-grown Rickettsia rickettsii. Thirty-four macaques became febrile and exhibited signs of infection ranging from transient illness with a few days of fever to severe illness with subsequent death. The rash appeared more frequently in the macaques inoculated subcutaneously.

Response of sublethally irradiated monkeys to a replicating viral antigen.

Temporal effects of exposure to sublethal, total-body X radiation (400 R) on responses to vaccination with attenuated Venezuelan equine encephalomyelitis vaccine virus. TC-83, were examined in rhesus monkeys. Viremia, often with delayed onset, was prolonged even when irradiation preceded vaccination by 28 days.

Treatment of influenza infection of mice by using rimantadine hydrochlorides by the aerosol and intraperitoneal routes.

Rimantadine hydrochloride was administered for 4 days in a small-particle (95% < 6.5 mum) aerosol (8.8 mg/kg per day) or intraperitoneally (40 mg/kg per day) to mice previously infected with influenza A/Aichi/2/68 (H(3)N(2)), mouse adapted.

Response of irradiated mice to live-virus (TC-83) immunization.

Studies were conducted to determine the effects of sublethal, acute, total-body irradiation (600 R) on the immune response of mice to a replicating antigen. Irradiation was performed at varying times (0 to 21 days) prior to immunization with attenuated Venezuelan equine encephalomyelitis virus, TC-83. Development of protective immunity was studied by inoculating subgroups of irradiated mice with virulent Venezuelan equine encephalomyelitis virus on days 1 through 28 after immunization.

Mechanisms of oral staphylococcal enterotoxin B-induced emesis in the monkey (38553).

Vomition is the most consistent response to oral SEB challenge in the monkey. The technique of cross-circulation clearly differentiates local neural phenomenon from humoral mechanisms. Our results support the theory that SED-induced vomition follows stimulation of local neural receptors in the gut.

Effects of antigen-antibody complexes on the primary immune response in Rhesus monkeys.

A model for the enhancement of the primary humoral immune response of rhesus monkeys to marginal or weakly antigenic vaccines is presented. Our procedure used the complexing of formalin-inactivated Venezuelan equine encephalomyelitis (VEE) virus vaccine with specific, homologous, immune gamma globulin (IgG) at equivalence. Equivalence was determined by combining the concentrated, isotopically labeled ((3)H) virus with various concentrations of specific Sephadex-fractionated IgG.

Yellow fever vaccine: direct challenge of monkeys given graded doses of 17D vaccine.

In rhesus monkeys a wide dosage range of 17D yellow fever (YF) vaccine extending to a level even below that recommended for vaccination of man elicited an immune response providing solid protection to challenge with virulent YF virus. Forty-three of 45 monkeys vaccinated with 10(2.3) or greater weanling mouse mean lethal doses of 17D vaccine were resistant to challenge 20 weeks later with virulent Asibi strain YF virus.

Transplacental transmission of Venezuelan equine encephalomyelitis virus in mice.

Transplacental infection of mouse fetuses with Venezuelan equine encephalomyelitis was produced by intraperitoneal injection of dams at various stages of gestation with 10(3) suckling mouse intracerebral median lethal doses of an attenuated strain (TC-83). Virus inoculation, at times ranging from 6 days prior to mating to 9 days after conception, had no effect on conception rate, litter size, or survival of the newborn. Inoculation of the dam from the 10th to 13th days of gestation resulted in decreased litter size, an increase in stillbirths, and a decrease in birth-to-weaning survival.