[Changes in telomere length in leukocytes of male rhesus macaques of different ages.]

Telomeres are specialized terminal sections of chromosomes that ensure the stability of the latter. DNA duplication during cell division is associated with telomere shortening due to the phenomenon of terminal underreplication. As cells divide, shortening of telomere length is considered to be one of the most important causes of cell aging. Estimation of telomere length still remains the subject of scientific research in gerontology and it is not used in clinical practice. Most often, rodents are used as a model object for studying the aging process, but the neuroendocrine mechanisms that influence, among other things, the regulation of the aging process differ in rodents and humans. The model objects closest in phylogenetic relation to humans are monkeys. In particular, Rhesus macaques is one of the representatives of the Old World most often used in biomedical research. However, data on age-related changes in telomere length in monkeys are extremely scarce. We studied the absolute average length of telomeres in DNA from blood leukocytes of 29 clinically healthy male rhesus monkeys aged from 4 to 24 years using quantitative PCR-method. The data obtained did not correspond to the normal distribution and the correlation analysis showed the absence of a significant dependence of telomere length on the age of the animals (rs=0,27; p>0,05). Thus, our study does not confirm the dependence of changes in the average length of telomeres of blood leukocytes with age.

Genotyping of Macaque Population on the Brain-Derived Neurotrophic Factor Gene Polymorphism by Mismatch Amplification Mutation Assay (MAMA)-PCR.

Human rs6265 (196G>A) polymorphism in the BDNF gene is associated with many clinically significant phenotypic manifestations. Rhesus monkey (Macaca mulatta) has a functionally significant rs309950446 ( 136G>A) polymorphism. To determine this polymorphism in macaques, we used mismatch amplification mutation assay (MAMA)-PCR method with non-complementary nucleotide to the template chain at the 3rd position from the 3'-end of the allele-specific primers (mismatch primers), which allowed the best discrimination of the alleles. Genotyping of male rhesus monkeys (n=178) and cynomolgus monkeys (Macaca fascicularis) (n=90) was carried out. The A/A, G/G, and G/A genotypes were found in 16, 34, and 50% rhesus macaques, respectively. In the cynomolgus macaques, the mutant polymorphic allele was not detected. The study results allow considering rhesus macaques as a potential biological model for assessment of the gen-environment interaction of the BDNF gene polymorphism.

[(ASSESSMENT OF RISK FOR ARBOVIRUS INFECTIONS IN RUSSIA)].

The sharply increased incidence and geographical expansion of arbovirus diseases in recent years suggest that some Russian areas are vulnerable to vector-borne diseases and that it is important to elaborate control programs to ensure bio- logical safety in our country. Moreover, the main vectors of the pathogens of arbovirus infections (Zika fever, dengue fever, chikungunya fevers), such as Aedes aegypti and Ae.albopictus, have been registered on the Black Sea coast of the Caucasus. The programs must be effective, by taking into account the biological features of each kind of a vector.

Transplantation of Simian Mesenchymal Stem Cells to Baboons with Experimentally Induced Myocardial Infarction.

Culture of mesenchymal stem cells isolated from the bone marrow of primates by their characteristics met the requirements of stem cells. It was shown that transplantation of allogeneic mesenchymal stem cells (2 million cells per 1 kg body weight) immediately after ligation of the left anterior descending coronary artery between the middle and upper thirds led to neovascularization and capillarization of the ischemic myocardium.

Potential Contribution of Cytomegalovirus Infection to Prenatal and Early Neonatal Mortality of Monkeys in the Adler Breeding Center.

Scrapings from the cervical canals and uterine cavities of females with a history of miscarriages, pathological deliveries, and stillbirths were tested for the cytomegalovirus DNA. The incidence of the agent in the females with a history of gestosis and abnormal deliveries was significantly higher than in females without anamnesis of this kind. Parenchymatous organs of stillborn neonates and animals dead during the first month of life were studied. This analysis and studies of the umbilical cords and placentas showed generalized cytomegalovirus infection in 22% dead animals, which objectively proved intrauterine infection.

[Efficiency of cycloferon against slow viral infection caused by SV-40 in monkeys and man].

The latent infection caused by Simian virus (SV-40) defeats monkeys and others animals. Currently there are not the prophylactic and therapeutic measures against this disease. We showed the infringement of immunity of M. mulatta infected by SV-40. The use of the preparation Cyclopheron for the treatment of this infection led to the normalization of the functions of immunity of monkeys and to disappearance of the virus from the organism. We suggested the new method for prophylaxis and treatment of latent SV-40 infection by Cyclopheron, may be used for the correction of the immunity.

Possible aspects of using cultured stem cell of laboratory primates in experimental medicine.

We describe the methods of isolation and culturing of mesenchymal stem cells from 3 monkey species Macaca mulatta, Papio hamadryas, and Macaca fascicularis. Flow cytofluorometry showed that the cells do not express CD34, CD45, and HLA-DR, but most of them (78-98%) express CD90 marker. The cardioprotective effects of cultured mesenchymal stem cells in cardiomyopathy induced by administration of antitumor anthracycline drugs (doxorubicin).

[Cycloferon therapy of cytomegalovirus infection in monkeys].

Cytomegalovirus (CMV) infection is a wide-spread disease throw humans and monkeys, which and associated with various diseases. The development of this infection in human organism is much like that in rhesus macaque, which makes CMV-infected monkeys adequate model for studying and elaborating prophylactic and therapeutic measures against this disease in humans. This article presents data on the efficiency of cycloferon action on animals with the M. mulatta CMV infection. Cycloferon stimulated an increase in the IFN-alpha production and promoted the period of remission in CMV-infected animals.

[Phylogenetic analysis of cytomegaloviruses isolated from man and different primate species].

Institute of Medical Primatology, Russian Academy of Medical Sciences, Sochi The conserved regions of nucleotide sequences were found in primate cytomegaloviruses (CMV). Universal primers were designed for the consensus sequence of a conservative region of the UL56 gene of the betaherpesvirinae subfamily. Amplification, sequencing, and phylogenetic analysis of the fragments of CMV strains isolated from man and different primate species were made. Analysis of sequenced gene fragments showed that the UL56 gene area is most suitable for the phylogenetic analysis of primate CMV and could identify several groups of clusters by the degree of relationship among the viruses of this family.

[Development of the PCR-test system for detection primate betaherpesvirinae].

A PCR-test system for detection of primate Betaherpesvirinae viruses was developed. Using alignment of complete genome of human, chimpanzee, and macaque rhesus cytomegalovirus conserve regions of viral genes were found. The oligonucleotide primers for consensus conserve regions of CMV UL56 gene were developed. The conditions of PCR were optimized and primer specificity for cytomegaloviruses of different primate species was confirmed.

Laboratory diagnosis of cytomegalovirus in monkeys in the Adler Breeding Center and in humans.

Monitoring of cytomegalovirus markers was carried out in the blood of humans and in the blood, lavage fluid specimens from the throat, and salivary gland tissues of monkeys of different species. Correlation between the percentage of cytomegalovirus infection and age was detected in humans. The virus was most often detected in salivary gland tissues and least so in the blood.

Parameters of the cytokine system functioning in laboratory primates.

The cytokine status (IFN, IL, etc.) of different monkey species (M. mulatta, P. hamadryas, C. aethiops) was studied. The interferon status is determined by the following parameters: IFN content in circulating blood and production of IFN-alpha and IFN-gamma by lymphocytes after appropriate in vitro induction. The interferon status of monkeys is similar to that of humans. The capacity to produce IFN reduces with age. It was found that genes of virtually all studied cytokines are expressed in blood cells and hence, in immune system cells.

[Phylogenetic analysis of the mycoplasma isolated from the Javanese macaque (M. fascicularis)].

The nucleotide sequence of the fragment of 16S-aRNA of mycoplasma was determined. The fragment was identified using the PCR method in the urogenital scrape of the Javanese macaque (M. fascicularis). The sequenced fragment of mycoplasma of M. fascicularis was compared to well-known sequences of mycoplasma of mammals. The results of our comparative and phylogenetic analyses of the sequenced DNA fragment revealed that the mycoplasma belonged to the M. primatum species and fell within the same cluster as M. hominis. The mycoplasma M. primatum was for the first time observed in the monkeys M. fascicularis. The pathogenicity of the mycoplasma species with respect to monkeys is being studied.