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Foamy virus evolution closely parallels that of the host species, indicating virus-host coadaptation. We studied simian foamy viruses (SFVs) from common marmosets, spider monkeys, and squirrel monkeys, New World monkey (NWM) species that share geographic ranges. The TRIM5alpha protein from each of these NWM species inhibited the replication of at least one of the SFVs associated with the other two species but did not affect the replication of its own SFV. Thus, TRIM5alpha has potentially shaped the evolution of SFVs in NWM hosts. Conversely, SFVs may have influenced the evolution of TRIM5 variants in New World primates.

We have previously shown that Plasmodium falciparum recombinant antigens PfEB200, R23, and Pfi72 inhibit opsonization of infected erythrocytes by hyperimmune Saimiri sera, indicating that they contain target epitopes involved in the phagocytosis of infected erythrocytes. We have investigated in this study the immune response of Saimiri monkeys with previous experience of malaria infections (preimmune monkeys) after injection of these recombinant antigens, administered alone or simultaneously. The humoral response to the recombinant antigens was monitored by radioimmunoassay, and the response to P. falciparum blood stages was assayed by immunofluorescence. The relative proportion of protective versus nonprotective immunoglobulin subtypes was investigated by using 3A2/G6 and 3E4/H8 monoclonal antibodies, and the capacity of the antisera to promote in vitro phagocytosis of infected erythrocytes was evaluated. The antigens evoked in most cases a secondary-type antibody response, resulting in important increases in antigen-specific antibody titers and concomitantly in anti-P. falciparum titers. The ratio of 3A2/G6 to 3E4/H8 immunoglobulin subtypes varied with the immunogen used. Opsonizing antibodies were boosted in several animals, the most promising combination being the mixture of PfEB200 and R23 that induced long-lasting production in five of five animals. The detectable opsonizing activity appearing after immunization of the animals was antigen specific, as it was lost after adsorption of the recombinant antigens. The challenge of the animals with blood stage parasites confirmed previous findings showing a correlation between the presence of detectable opsonizing antibodies in serum and protection.

Herpesvirus saimiri (HVS) is a lymphotropic herpesvirus that induces T-cell transformation in vitro and causes lymphomas and leukemias in New World primates other than its natural host, the squirrel monkey. Nucleotide sequence analysis of the HVS genome revealed two open reading frames with significant homology to genes for human complement regulatory molecules. One of these genes encodes a predicted protein (designated HVSCD59) with 48% amino acid sequence identity to the human terminal complement regulatory protein CD59 (HuCD59). The CD59 homolog from squirrel monkey (SMCD59) was cloned, and the corresponding amino acid sequence showed 69% identity with HVSCD59. BALB/3T3 cells stably expressing HVSCD59, SMCD59, or HuCD59 were equally protected from complement-mediated lysis by human serum. However, only HVSCD59-expressing cells were effectively protected from complement-mediated lysis when challenged with rat serum, suggesting that HVSCD59 was less species restrictive. The complement regulatory activity of HVSCD59 and SMCD59 occurred after C3b deposition, indicating terminal complement inhibition. Treatment of BALB/3T3 stable transfectants with phosphatidylinositol-specific phospholipase C prior to complement attack decreased the complement regulatory function of HVSCD59, suggesting cell surface attachment via a glycosyl-phosphatidylinositol anchor. Cells expressing HVSCD59 effectively inhibited complement-mediated lysis by squirrel monkey serum in comparison with SMCD59-expressing cells. Finally HVSCD59-specific transcripts were detected in owl monkey cells permissive for lytic HVS replication but not in T cells transformed by HVS, which failed to produce virions. These data are the first to demonstrate a functional, virally encoded terminal complement inhibitor and suggest that HVSCD59 represents a humoral immune evasion mechanism supporting the lytic life cycle of HVS.

The new-world monkeys Saimiri sciureus (squirrel monkeys) are currently used as a model to test the efficacy of vaccines against human malaria. To improve our knowledge on this model, we tested the susceptibility of S. sciureus B cells to Epstein-Barr virus (EBV) infection. B-lymphoblastoid cell lines were obtained from six of six healthy animals after infection with the B95-8 source of EBV. The frequency distributions of spleen B cells clonally committed to the production of immunoglobulins M and G, as measured by limiting dilution analysis, were from 1 in 179 to 1 in 1,085 and from 1 in 45 to 1 in 60, respectively, in three monkeys naturally infected with Plasmodium brasilianum. In the same three animals, the frequency of spleen B cells committed to the production of P. brasilianum-specific antibody ranged from 1 in 2,211 to 1 in 9,099. One B-lymphoblastoid cell line producing anti-P. brasilianum-specific antibody was cloned twice, and the immunoglobulin G produced was purified. This monoclonal antibody recognized a parasite component of 197 kDa and was specific for Plasmodium malariae and P. brasilianum parasites. These data document that squirrel monkey B cells naturally primed by an infectious agent can be efficiently used to produce monospecific antibodies against the infectious agent.

Herpesvirus saimiri is a horizontally transmitted virus of squirrel monkeys (Saimiri sciureus) which, when inoculated into owl monkeys (Aotus trivirgatus), induces fatal malignant lymphoma in 75 to 80% of the animals. Previous immunological and virological studies have not indicated why 20 to 25% of inoculated owl monkeys develop a chronic, disease-free H. saimiri infection. In the present study, we examined two parameters to explain why certain owl monkeys are resistant to H. saimiri-induced disease. The first possibility was that the animals in which H. saimiri established a chronic infection were all of the same karyotypic class. In studying four such animals, we found that three of the seven known karyotyes were represented, indicating that chromosome polymorphism does not explain disease resistance. The second possibility examined was that animals which develop disease do so as a result of a failure in specific anti-H. saimiri cell-mediated immunity. Naturally infected squirrel monkeys exhibited long-lasting, virus-specific cell-mediated immunity in a lymphocyte proliferation assay, whereas such reactivity could not be demonstrated either in chronically infected owl monkeys or in an owl monkey with a primary H. saimiri infection. The failure of owl monkeys to respond to viral antigens was not due to a basic immunological defect, since these animals gave normal responses to heterologous cells and were capable of being sensitized with the protein antigen keyhole limpet hemocyanin.

Protective immunity against Plasmodium falciparum malaria in the squirrel monkey (Saimiri sciureus) is, in part, antibody mediated. We have previously shown that polypeptides of 41, 76, and 96 kilodaltons (kDa) are specifically immunoprecipitated with monkey sera which are protective in passive transfer experiments. We report here that three different 96-kDa polypeptides, of pI 5.15, 5.25, and 5.35, can be visualized when parasite extracts are analyzed in bidimensional gels. Only one of them (of pI 5.25) was stable after being heated at 100 degrees C for 5 min. The 96-kDa thermostable polypeptide of pI 5.25 was immunoprecipitated by protective monkey sera and by sera from adult humans living in hyperendemic areas and thus seems to be correlated with humoral protective immunity. This antigen was found in culture supernatants at the time of schizont rupture. It was synthesized during the schizont stage and is apparently not a glycoprotein.

A procedure is described for the routine laboratory diagnosis of viral serum antibodies. Antigens are dotted on nitrocellulose strips or sheets, and sera are applied on absorbent paper strips. Antigen-antibody complexes are detected with enzyme-conjugated antiglobulin and development of a colored, insoluble substrate product. The test allows processing of multiple sera in one 3- to 5-h operation and is equal to or more sensitive than serum neutralization, hemagglutination inhibition, and fluorescent antibody assays. Highly infectious viruses inactivated with a psoralen derivative and long-wavelength UV light irradiation can be used as antigens, allowing the study of human pathogens. Although the test detects cross-reacting, group-specific herpesvirus antigens, the intensity of the antibody reaction is greatest with type-specific antigens. Preliminary data suggest that the technique will be useful for the rapid typing of viruses from clinical specimens.

The objective of this study was to determine whether the squirrel monkey (Saimiri scuireus) is indigenously colonized with black-pigmented bacteroides (BPB) resembling human Bacteroides gingivalis and Bacteroides intermedius (suspected periodontal pathogens) and to determine the usefulness of the squirrel monkey as an in vivo model for studying colonization by putative pathogens. We assayed the subgingival plaques of 138 monkeys of various ages and in four different colonies for the presence of anaerobic BPB microorganisms. We also tested half the animals for the presence of Actinobacillus actinomycetemcomitans. Clinical indices and levels of serum antibody to B. gingivalis were recorded. We detected BPB in 50% of the animals and A. actinomycetemcomitans in 69% of the animals. The presence of BPB was generally associated with increased age, increased gingival index, presence of calculus, and increased levels of serum antibody. These data indicate that the squirrel monkey may be a good model for studying the parameters of natural infection of the gingival crevice with suspected periodontopathogenic BPB microorganisms.