Transmission of simian acquired immunodeficiency syndrome (SAIDS) with blood or filtered plasma

Simian acquired immunodeficiency syndrome (SAIDS), a disease clinically and pathologically similar to acquired immunodeficiency syndrome in humans, was transmitted from diseased rhesus monkeys (Macaca mulatta) to normal monkeys by inoculation with heparinized whole blood or plasma that had been passed through filters of 0.45 micrometer pore size. This suggests that the causative agent is small and most probably a virus. No viruses, however, were isolated by standard cell culture techniques from the blood or filtered plasma which caused SAIDS. Both cellular and humoral immunity were markedly depressed in animals with advanced SAIDS.     

Nucleotide sequence of SRV-1, a type D simian acquired immune deficiency syndrome retrovirus

Simian acquired immune deficiency syndrome (SAIDS) in the macaque genus of monkeys at the California Primate Research Center is apparently caused by infection by a type D retrovirus. The complete nucleotide sequence (8173 base pairs) of a molecular clone of the prototype SAIDS virus isolate, SRV-1, reveals a typical retrovirus structure with long terminal repeats (346 base pairs) and open reading frames for the gag (663 codons), pol (867 codons), and env (605 codons) genes. SRV-1 also has a separate open reading frame of 314 codons between the gag and pol genes that defines the viral protease gene (prt) and a short open reading frame of unknown significance downstream from the env gene. The SRV-1 protease region shows a high degree of homology to its counterpart in the hamster intracisternal A-type particle genome; both these protease genes are about twice as long as the analogous region of other retroviruses. SRV-1 has no notable similarity in either genetic organization or sequence to the human AIDS retroviruses.     

EXPERIMENTAL AIR-BORNE INFECTION WITH POLIOMYELITIS VIRUS

Infection has been obtained in both rhesus and cynomolgus monkeys by inhalation of poliomyelitis virus in the form of droplet nuclei. The olfactory route was excluded in part of the animals successfully infected. The gastrointestinal route is believed to have been excluded in the rhesus monkeys. It seems most probable that the portals of entry were the lower respiratory mucosa in the case of the rhesus monkeys and the oropharyngeal mucosa in the case of the cynomolgus monkeys. Fever and occasional mild symptoms in 8 other rhesus monkeys suggest that an abortive form of poliomyelitis may have resulted from inhalation, but this can not at present be considered as proved. The experiments open up the possibility that human poliomyelitis may, at least sometimes, be an air-borne infection and that the lungs may be a portal of entry. Neither of these aspects of the disease has hitherto, so far as we are aware, been studied experimentally. The presence of virus in the human nasopharynx, which has been repeatedly demonstrated,(7, 8) provides an obvious source of air contamination by patients and carriers; and direct contact has been traced during epidemics in a considerable fraction of cases,(9) amounting to about one third in the report of Top and Vaughan.(10) The relative importance of transmission by air and by ingested material remains to be determined. It would seem probable, however, that both modes of infection must be taken into account.     

A new type D retrovirus isolated from macaques with an immunodeficiency syndrome

Macaque monkeys with the recently described acquired immunodeficiency syndrome show a marked defect in T-lymphocyte function and die with opportunistic infections and lymphoproliferative abnormalities. In the study described here a new type D retrovirus was isolated from two Macaca cyclopis with this syndrome. This virus is related to, but distinct from, Mason-Pfizer monkey virus, a type D retrovirus previously isolated from a mammary tumor of a rhesus monkey (Macaca mulatta).     

Subhuman primate diploid cells: possible substrates for production of virus vaccines

Results of a program for development of new cell lines suggest that it it possible to establish cell lines from both rhesus and African green monkeys which are comparable to diploid lines of human origin, and that these monkey lines should be candidates for use in the production of virus vaccines.     

A formalin-inactivated whole SIV vaccine confers protection in macaques

A vaccine against human immunodeficiency virus (HIV) would be highly effective in stopping the acquired immunodeficiency syndrome (AIDS) epidemic. A comprehensive evaluation of potential vaccine methodologies can be made by means of the simian model for AIDS, which takes advantage of the similarities in viral composition and disease potential between simian immunodeficiency virus (SIV) infection of rhesus macaques and HIV infection in humans. Immunization with a formalin-inactivated whole SIV vaccine potentiated with either alum and the Syntex adjuvant threonyl muramyl dipeptide (MDP) or MDP alone resulted in the protection of eight of nine rhesus monkeys challenged with ten animal-infectious doses of pathogenic virus. These results demonstrate that a whole virus vaccine is highly effective in inducing immune responses that can protect against lentivirus infection and AIDS-like disease.     

Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease

Lentiviral delivery of glial cell line-derived neurotrophic factor (lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models of Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra of nonlesioned aged rhesus monkeys or young adult rhesus monkeys treated 1 week prior with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive GDNF expression with anterograde and retrograde transport was seen in all animals. In aged monkeys, lenti-GDNF augmented dopaminergic function. In MPTP-treated monkeys, lenti-GDNF reversed functional deficits and completely prevented nigrostriatal degeneration. Additionally, lenti-GDNF injections to intact rhesus monkeys revealed long-term gene expression (8 months). In MPTP-treated monkeys, lenti-GDNF treatment reversed motor deficits in a hand-reach task. These data indicate that GDNF delivery using a lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients.     

POLIOMYELITIS VIRUS IN FLY-CONTAMINATED FOOD COLLECTED AT AN EPIDEMIC

Poliomyelitis virus has been detected in food exposed to flies at homes of poliomyelitis patients within an epidemic area. This was achieved by feeding such exposed food to chimpanzees which developed subclinical infections or asymptomatic carrier states ascertained by positive stool tests in rhesus monkeys.     

Behavioral effects in monkeys of racemates of two biologically active marijuana constituents

Both dl-Delta(8)- and dl-Delta(9)-tetrahydrocannabinol produced marked alterations of behavior in rhesus and squirrel monkeys. Squirrel monkeys appeared to have visual hallucinations. Continuous avoidance behavior of squirrel monkeys was stimulated by both drugs, but high doses of dl-Delta(9)-tetrahydrocannabinol also caused depression after the stimulant phase. Complex behavior involving memory and visual discrimination in rhesus monkeys was markedly disrupted by both drugs.     

Induction of AIDS in rhesus monkeys by molecularly cloned simian immunodeficiency virus

Better understanding of the pathogenesis of acquired immunodeficiency syndrome (AIDS) would be greatly facilitated by a relevant animal model that uses molecularly cloned virus of defined sequence to induce the disease. Such a system would also be of great value for AIDS vaccine research. An infectious molecular clone of simian immunodeficiency virus (SIV) was identified that induces AIDS in common rhesus monkeys in a time frame suitable for laboratory investigation. These results provide another strong link in the chain of evidence for the viral etiology of AIDS. More importantly, they define a system for molecular dissection of the determinants of AIDS pathogenesis.     

Application and Assessment of Ketamine-Xylidinothiazoline Combinations for Anaesthesia in Rhesus Monkey

The quantitative anaesthesia assessment technique was used to evaluate the effectiveness of ketamine, ketamine-xylidinothiazoline in rhesus monkey. Total 20 healthy adult rhesus monkeys were divided into two groups and anaesthetized using either intramuscular （IM） ketamine （20 mg·kg^-1） or ketamine （5 mg·kg^-1 IM） and xylidinothiazoline （1 mg·kg^-1 IM）. During anaesthesia rectal temperature, respiratory rate, heart rate, saturation of blood oxygen and blood pressure were recorded. The degree of sedation, analgesia, muscle relaxation were monitored either. The results showed that ketamine alone did not produce adequate anaesthesia, and the combination of xylidinothiazoline and ketamine provided adequate anesthesia for rhesus monkeys with no significant side effects and little effects on respiration and circulation.     

Tolerance develops to the disruptive effects of delta 9-tetrahydrocannabinol on primate menstrual cycle

Long-term exposure of sexually mature female rhesus monkeys (Macaca mulata) to thrice weekly injections of delta 9-tetrahydrocannabinol resulted in a disruption of menstrual cycles that lasted for several months. This period was marked by an absence of ovulation and decreased basal concentrations of gonadotropin and sex steroids in the plasma. After this period, normal cycles and hormone concentrations were reestablished. These studies demonstrate that in rhesus monkeys subjected to long-term treatment with delta 9-tetrahydrocannabinol tolerance develops to the disruptive effects of the drug on the menstrual cycle.     

Preventing AIDS but not HIV-1 infection with a DNA vaccine

Although there has been some success in treating human immunodeficiency virus (HIV) patients with triple drug therapy (highly active antiretroviral therapy or HAART), the best hope for combating AIDS (the disease caused by HIV) could be a combination of drug therapy and vaccination, according to Shen and Siliciano in their Perspective. A new study in rhesus monkeys treated with a DNA vaccine (Barouch et al.) demonstrates that a powerful vaccine-induced CD8(+) cytolytic T cell response reduces the amount of virus in the blood to very low levels preventing the drastic decrease in CD4(+) T helper cells and subsequent immunodeficiency. As the Perspective authors explain, vaccinating HIV patients that are receiving HAART may enable HIV levels to be permanently brought under control such that the drug treatment can eventually be stopped.     

Hyperphagia and polydipsia in socially isolated rhesus monkeys

Three rhesus monkeys which had been isolated from social contact during their first year of life persistently overate and overdrank during adulthood. These monkeys ingested approximately twice as much fluid and food as the control animals reared normally.     

Nalorphine: increased sensitivity of monkeys formerly dependent on morphine

Three rhesus monkeys Macaca mulatta, formerly dependent on morphine, had increased sensitivity to nalorphine's effect of suppressing operant responding for food, as compared with two monkeys with no history of morphine exposure. Within the dose range employed, nalorphine injections produced emesis, salivation, and hyperirritability in formerly morphine-dependent monkeys but not in controls.     

Thalidomide: effect upon pregnancy in the rhesus monkey

Thalidomide was administered to 44 female rhesus monkeys immediately after they had mated. There were no live births from these animals, whereas there were 11 live births in 57 untreated monkeys. The results are statistically significant. The hypothesis is advanced that thalidomide killed the embryo prior to implantation.     

Tumors induced in primates by chicken sarcoma virus

A suspension of a variant of Rous sarcoma was injected into four adult and eight newborn rhesus monkeys. Seven newborns developed tumors, three of which were diagnosed as fibrosarcomas, in 2 to 6 weeks; none of the adults have tumors after 11 weeks. Virus was demonstrated in two of the tumors by injecting a tumor-suspension preparation into the chick wing-web where tumors subsequently appeared. To the best of our knowledge this is the first time that sarcomas have developed in primates after a virus has been injected.     

Experimental leprosy in three species of monkeys

Eleven mangabey monkeys inoculated with Mycobacterium leprae developed lepromatous-type leprosy. Nine of the mangabeys were inoculated with M. leprae isolated from a mangabey with naturally acquired lepromatous leprosy. Immune function was depressed in some of these animals after dissemination of the disease. Two mangabeys developed lepromatous leprosy after inoculation with human M. leprae passaged in an armadillo. Three rhesus and three African green monkeys inoculated with mangabey-derived M. leprae also developed lepromatous leprosy. Mangabeys may be the first reported nonhuman primate model for the study of leprosy. Rhesus and African green monkeys may also prove to be reproducibly susceptible to the disease.