The genetic evolution of the envelope gene of simian immunodeficiency virus in cynomolgus macaques infected with a complex virus pool.

Two cynomolgus macaques were infected with a complex, but characterized, challenge stock of simian immunodeficiency virus (SIVmac251 32H). The polymerase chain reaction was applied in a temporal sequence analysis to determine the sequences of the gp120 region of the SIV env gene, which were present in the blood of both macaques at 1, 6, and 15 months postinfection (p.i.). At 1 month p.i. selected sequences, which had been present in the original virus challenge stock, were reisolated. At later times, new sequences emerged, which had not been detected in the original virus challenge stock. Changes in sequence were restricted to specific regions of gp120, notably those equivalent to V1, V2, V4, and V5 of HIV-1, but not V3. The diversity and the rate of appearance of new sequences in the V1 region suggest that genetic evolution occurs by mechanisms in addition to nucleotide substitutions. These results are discussed in relation to the role of the envelope protein in the generation of protective immunity against infection with immunodeficiency viruses.

Mapping of mutations associated with neurovirulence in monkeys infected with Sabin 1 poliovirus revertants selected at high temperature.

Poliovirus type 1 neurovirulence is difficult to analyze because of the 56 mutations which differentiate the neurovirulent Mahoney strain from the attenuated Sabin strain. We have isolated four neurovirulent mutants which differ from the temperature-sensitive parental Sabin 1 strain by only a few mutations, using selection for temperature resistance: mutant S(1)37C1 was isolated at 37.5 degrees C, S(1)38C5 was isolated at 38.5 degrees C, and S(1)39C6 and S(1)39C10 were isolated at 39.5 degrees C. All four mutants had a positive reproductive capacity at supraoptimal temperature (Rct+ phenotype). Mutant S(1)37C1 induced paralysis in two of four cynomolgus monkeys, and the three other mutants induced paralysis in four of four monkeys. The lesion score increased from the S(1)37C1 mutant to the S(1)39 mutants. To map the mutations associated with thermoresistance and neurovirulence, we sequenced all regions in which the Sabin 1 genome differs from the Mahoney genome. The S(1)37C1 mutant had one mutation in the 5' noncoding region and another in the 3' noncoding region. Mutant S(1)38C5 had these mutations plus another mutation in the 3D polymerase gene. The S(1)39 mutants had three additional mutations in the capsid protein region. The mutations were located at positions at which the Sabin 1 and Mahoney genomes differ, except for the mutation in the 5' noncoding region. The noncoding-region mutations apparently confer a low degree of neurovirulence. The 3D polymerase mutation, which distinguishes S(1)38C5 and S(1)39 mutants from S(1)37C1, is probably responsible for the high neurovirulence of S(1)38C5 and S(1)39 mutants. The capsid region mutations may contribute to the neurovirulence of the S(1)39 mutants, which was the highest among the mutants.

Molecular pathogenesis of neural lesions induced by poliovirus type 1.

Using in situ hybridization techniques for viral RNA and employing a specific riboprobe, we have detected virus in neural cells of monkeys infected with poliovirus type 1 (PV-1) by the intraspinal route. In monkeys paralysed after inoculation of a neurovirulent revertant of PV-1/Sabin strain, viral RNA was detected in motor neurons and their processes, and in polymorphonuclear and small neural cells. Quantitative in situ hybridization provided evidence of viral replication in individual cells suggesting that the death of motor neurons was due to the direct effect of poliovirus replication in these cells. The histological study of neural lesions of monkeys paralysed after infection with the attenuated Sabin strain of PV-1 revealed two major differences compared to monkeys infected with a virulent strain: (i) the number of destroyed motor neurons was reduced and limited to the site of inoculation and (ii) the inflammatory reaction was localized but more intense. An account is given of the difference in histopathology induced by virulent and attenuated strains of PV-1 in the central nervous system.

Susceptibility of tamarin (Saguinus labiatus) red blood cell membrane lipids to oxidative stress: implications for wasting marmoset syndrome.

Captive Callitrichids frequently suffer a fatal wasting disease, wasting marmoset syndrome (WMS), of unexplained cause. This paper describes studies on the erythrocytes from animals in a breeding colony of tamarins (Saguinus labiatus), in which deaths from anaemia and wasting were occurring, to seek evidence for biochemical changes which could lead to oxidative damage and premature cell lysis. In only one animal of 33 studied did the red blood cell lipids show an increased susceptibility to oxidative damage. This animal, with some degree of certainty, could be diagnosed as having WMS. It was concluded that evidence for a primary deficiency of antioxidants as a cause of unexplained deaths, or WMS, in the colony could not at present be substantiated.

Scoliosis caused by section of dorsal spinal nerve roots.

Experimental evidence has accumulated in recent years to suggest that scoliosis can be caused by asymmetrical spinal muscle weakness due to sensorineural loss, though this suggestion has not achieved universal acceptance. The evidence is supported by histopathological observations on cases of clinical idiopathic scoliosis. A study is presented in which cynomolgus monkeys had one, two or three dorsal spinal nerve roots cut. Scoliosis developed, convex to the damaged side; its severity was dependent on the number of nerve roots cut. Section of the first lumbar dorsal spinal nerve root had a marked tendency to cause scoliosis. The study supports the view that scoliosis may be caused by asymmetrical paraspinal muscle weakness acting through loss of proprioception.

An outbreak of Yersinia pseudotuberculosis infection in a small indoor breeding colony of red-bellied (Saguinus labiatus) tamarins.

A spontaneous outbreak of yersiniosis caused by Yersinia pseudotuberculosis serotype IIB occurred in a small indoor breeding colony of red-bellied tamarins (Saguinus labiatus) during the winter of 1981. Of 35 monkeys at risk 6 died of an acute or subacute infection over a period of 23 days. Clinical signs were anorexia, weakness, listlessness and depression. The disease was characterized by focal necrosis of the liver, spleen, mesenteric lymph nodes, ulcerative enteritis, and the presence of colonies of Gram-negative bacilli in the lesions. Y. pseudotuberculosis was isolated from the liver, spleen, mesenteric lymph nodes and kidney but not from the blood, lung or intestine. Contaminated food was believed to be the source of infection.

Red-bellied tamarins (Saguinus labiatus): Hematologic reference values and hemopathologic responses.

Hematologic reference values have been established for captive adult red-bellied tamarins (Saguinus labiatus) by carrying out full blood counts and fibrinogen estimations on 25 clinically normal animals. The only significant sex difference detected was in the reticulocyte count which was higher in females than in males. The reference values were used to identify abnormal changes in the blood of nine clinical cases. Hypochromic anemia, neutrophilia, and raised fibrinogen levels were found in animals with self-inflicted injuries, dermatitis, and ileocecal intussusception. Target cells and jaundiced plasma were noted in a case of yersiniosis. Two animals in which generalized muscle wasting was the main abnormal clinical sign were severely anemic, and in one of these cases a significant number of Heinz bodies was present. The findings in these two animals were compared with those in common marmosets (Callithrix jacchus) with possible wasting marmoset syndrome.

Experimental scoliosis in primates: a neurological cause.

Although a variety of techniques have been used with varying success to induce scoliosis in animals, primates have rarely been used. A series of monkeys is presented where scoliosis developed incidentally during the routine virulence testing of live, attenuated, oral poliomyelitis vaccines by intraspinal injection. The site and extent of histological damage in the different anatomical areas of the spinal cord were examined in 25 scoliotic monkeys and 25 matched controls. Analysis of the data demonstrated that there was significantly greater damage on the convex side of the spinal cords of the scoliotic animals, particularly in the sensory areas-the posterior horn and Clarke's column. Scoliosis was not thought to be caused by clinical poliomyelitis as the involvement of the anterior horn was not significantly greater than in the scoliotic animals than in the controls. These observations are taken to support the view that scoliosis may develop as a result of asymmetrical weakness of the paraspinal muscles due to the loss of proprioceptive innervation.

Pinworm infections in laboratory rodents: a review.

The important and common oxyurids which affect laboratory rodents- Syphacia spp., Aspiculuris tetraptera and Passalurus ambiguus-are discussed and reviewed. Their life histories, pathogenicity and immunity are examined, and mention is made of the influence of age, sex, strain and host status on infection. The importance of using worm-free animals in experimental work is stressed, and guidance is given on diagnosis and control.