Sığır Lösemi Virüsü ile Enfekte Sığırlarda Telomer Uzunluğu ile Fizyolojik Parametreler Arasındaki İlişkinin Değerlendirilmesi

Öz

Çalışmanın amacı, sığır lökozis virüsü ile enfekte sığırlarda göreceli telomer uzunlukları ile çeşitli fizyolojik parametreler arasındaki ilişkiyi araştırmak ve Türkiye'deki süt sığırlarında sığır lökozis virüsü enfeksiyonu ile ilişkili risk faktörlerini belirlemektir. Risk değerlendirmesi için yaş, doğum sayısı ve vücut kondisyon skoru olmak üzere üç değişken kullanılmıştır. Sığır lökozis virüsüne özgü antikorlar enzim bağlı immünosorbent testi kullanılarak tespit edilmiş ve göreceli telomer uzunlukları polimeraz zincir reaksiyonu ile ölçülmüştür. En yüksek seropozitiflik oranı (%39,13), vücut kondisyon skoru 3-3,5 olan ve 2-8 yaş arasındaki sığırlarda gözlenmiştir. Göreceli telomer uzunluğunun seropozitiflik, ileri yaş ve doğum sayısı ile pozitif korelasyonlu olduğu, seropozitiflik ile vücut kondisyon skoru arasında ise negatif korelasyon olduğu bulunmuştur. Sığır lökozis virüsü ile enfekte sığırlardaki göreceli telomer uzunlukları, enfekte olmayan sığırlara kıyasla anlamlı derecede daha kısa (P < 0,05) bulundu. Vücut kondisyon skoru grupları arasında en kısa göreceli telomer uzunlukları, vücut kondisyon skoru ≤ 2,5 olan sığır lökozis virüsü ile enfekte sığırlarda ve vücut kondisyon skoru 3-3,5 olan enfekte olmayan sığırlarda bulundu. Yaş gruplarına gelince, en kısa göreceli telomer uzunlukları, 8 yaşından büyük sığır lökozis virüsü ile enfekte sığırlarda (P < 0,05) ve aynı yaş grubundaki enfekte olmayan sığırlarda (P < 0,05) gözlendi. Sonuç olarak, sığır lökozis virüsü ile enfekte sığırlardaki göreceli telomer uzunluklarının, enfekte olmayan sığırlara kıyasla anlamlı derecede daha kısa olduğu bulundu (P < 0,05). En kısa göreceli telomer uzunlukları hem sığır lökozis virüsüyle enfekte olmuş hem de enfekte olmamış 8 yaş üstü sığırlarda kaydedildi (P < 0,05). Son olarak, sığır lökozis virüsü enfeksiyonu ile göreceli telomer uzunlukları arasındaki ilişki, yaş, doğum sayısı ve vücut kondisyon skoru gibi diğer faktörlerle birlikte, hastalık kontrolü ve önleme programları için yararlı olabileceği kanısına varıldı.

Anahtar Kelimeler

• Yaş
• Vücut kondisyon skoru
• Sığır lökozis virüsü
• Doğum sayısı
• Göreceli telomer uzunluğu

Assessment of The Relationship Between Telomere Length and Physiological Parameters in Cattle Infected with Bovine Leukosis Virus

Öz

The study aims to investigate the relationship between relative telomere lengths and various physiological parameters in cattle infected with bovine leukosis virus, as well as to identify the risk factors associated with cow-level bovine leukosis virus infection in dairy cattle in Türkiye. Three variables—age, parity, and body condition score—were used for risk assessment. Antibodies specific to bovine leukosis virus were detected using an enzyme-linked immunosorbent assay, and relative telomere lengths were measured by polymerase chain reaction. The highest seropositivity rate (39.13%) was observed in cattle with a body condition score of 3–3.5 and aged between 2–8 years. relative telomere length was found to be positively correlated with seropositivity, advanced age, and parity, while a negative correlation was observed between seropositivity and body condition score. Relative telomere lengths in bovine leukosis virus-infected cattle were significantly shorter (P < 0.05) than those in non-infected cattle. Among body condition score groups, the shortest relative telomere lengths were found in bovine leukosis virus-infected cattle with body condition score ≤ 2.5 and in non-infected cattle with body condition score 3–3.5. Regarding age groups, the shortest relative telomere lengths were observed in bovine leukosis virus-infected cattle older than 8 years (P < 0.05), as well as in non-infected cattle of the same age group (P < 0.05). In conclusion, relative telomere lengths in bovine leukosis virus-infected cattle were found to be significantly shorter than in non-infected cattle (P < 0.05). The shortest relative telomere lengths were recorded in both bovine leukosis virus-infected and non-infected cattle over 8 years of age (P < 0.05). Finally, the association between bovine leukosis virus infection and relative telomere lengths, along with other factors such as age, parity, and body condition score, is considered potentially useful for disease control and prevention programs.

Anahtar Kelimeler

• Age
• Body condition score
• Bovine leukosis virus
• Parity
• Relative telomere length

Kaynakça

1. Aida Y., Murakami H., Takahashi M., Takeshima SN. Mechanisms of pathogenesis induced by bovine leukemia virus as a model for human T-cell leukemia virus. Frontiers in Microbiology 2013; 4: 328.
2. Armanios M., Blackburn EH. The telomere syndromes. Nature Reviews Genetics 2012; 13(10): 693-704.
3. Avcı O., Bulut O., Yapıcı O., Atlı K., Dik I. Sütçü ineklerin kan ve süt serumlarında bovine leukosis virus enfeksiyonunun ELISA ile araştırılması. Erciyes Üniversitesi Veteriner Fakültesi Dergisi 2013; 10(3): 171-176.
4. Ayvazoğlu C., Akyüz E., Kızıltepe Ş., Gökçe G. Investigation of the prevalence of enzootic bovine leukosis in cattle in Ardahan region. Journal of Advances in VetBio Science and Techniques 2021; 7(1): 1-7.
5. Batmaz H., Carli KT., Kahraman M., Cetin C., Kennerman E. Serological and haematological diagnosis of enzootic bovine leukosis in cattle in Turkey. The Veterinary Record 1995; 136(2): 42-44.
6. Blackburn EH. Structure and function of telomeres. Nature 1991; 350(6319): 569-573.
7. Brenner J., Van-Haam M., Savir D., Trainin Z. The implication of BLV infection in the productivity, reproductive capacity and survival rate of a dairy cow. Veterinary Immunology and Immunopathology 1989; 22(3): 299-305.
8. Burgu I., Urman HK., Kaaden OR., Truyen U., Akça Y., Alcigir G., Berkin S., Alkan F., Atasever A. Sero-epidemiological and pathological studies on enzootic bovine leukosis in Turkey. DTW. Deutsche tierarztliche Wochenschrift 1991; 98(6): 226-228.

9. Camargos MF., Stancek D., Rocha MA., Lessa LM., Reis JKP., Leite RC. Partial sequencing of env gene of bovine leukaemia virus from Brazilian samples and phylogenetic analysis. Journal of Veterinary Medicine, Series B 2002; 49(7): 325-331.
10. Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Research 2002; 30(10): e47-e47.
11. Chebel A., Bauwens S., Gerland LM., et al. Telomere uncapping during in vitro T-lymphocyte senescence. Aging Cell 2009; 8(1): 52-64.
12. Counter CM., Botelho FM., Wang P., Harley CB., Bacchetti S. Stabilization of short telomeres and telomerase activity accompany immortalization of Epstein-Barr virus-transformed human B lymphocytes. Journal of Virology 1994; 68(5): 3410-3414.
13. Dewulf M., Pascottini OB., Heirbaut S., et al. Shortening of the telomere length during the transition period of dairy cows in relation to biological stress. Scientific Reports 2024; 14(1): 31756.
14. Dewulf M., Duchateau L., Meesters M., et al. Telomere length in neonatal dairy calves in relation to lifetime parameters. Animals 2025; 15(1): 109.
15. Dogan F., Bilge DS., Dik B., Farzani TA., Alkan F. Detection of genotype 1 bovine leukemia virus from a C. schultzei pool: Do Culicoides spp. have a role on the transmission of bovine leukemia virus?. Infection, Genetics and Evolution 2020; 85: 104469.
16. Erskine RJ., Bartlett PC., Byrem TM., Render CL., Febvay C., Houseman JT. Association between bovine leukemia virus, production, and population age in Michigan dairy herds. Journal of Dairy Science 2012; 95(2): 727-734.
17. Evermann JF., DeAvila DM., Parish SM., et al. Evaluation of a serum ELISA for detection of bovine leukemia viral antibodies in milk samples. Journal of Veterinary Diagnostic Investigation 2019; 31(4): 598-600.
18. Gil ME., Coetzer TL. Real-time quantitative PCR of telomere length. Molecular Biotechnology 2004; 27(2): 169-172.
19. Greider CW., Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 1985; 43(2): 405-413.
20. Hady PJ., Domecq JJ., Kaneene JB. Frequency and precision of body condition scoring in dairy cattle. Journal of Dairy Science 1994; 77(6): 1543-1547.
21. Haghparast A., Tabatabaiezadeh E., Mohammadi G., Kord N. Prevalence of bovine leukemia virus (BLV) antibodies in bulk tank milk of dairy cattle herds of Mashhad area, north-east of Iran. Journal of Animal and Veterinary Advances 2012; 11(2): 276-280.
22. Hemann MT., Strong MA., Hao LY., Greider CW. The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 2001; 107(1): 67-77.
23. Hemmatzadeh F., Keyvanfar H., Hasan NH., et al. Interaction between bovine leukemia virus (BLV) infection and age on telomerase misregulation. Veterinary Research Communications 2015; 39(2): 97-103.
24. Hiyama K., Hiyama E., Ishioka S., et al. Telomerase activity in small-cell and non-small-cell lung cancers. Journal of the National Cancer Institute 1995; 87(12): 895-902.
25. Kettmann R., Portetelle D., Mammerickx M., et al. Bovine leukemia virus: an exogenous RNA oncogenic virus. Proceedings of the National Academy of Sciences 1976; 73(4): 1014-1018.
26. Ladronka RM., Ainsworth S., Wilkins MJ., Norby B., Byrem TM., Bartlett PC. Prevalence of bovine leukemia virus antibodies in US dairy cattle. Veterinary Medicine International 2018; 2018(1): 5831278.
27. Lu W., Zhang Y., Liu D., Songyang Z., Wan M. Telomeres-structure, function, and regulation. Experimental Cell Research 2013; 319(2): 133-141.
28. Meesters M., Van Eetvelde M., Martens DS., Nawrot TS., et al. Prenatal environment impacts telomere length in newborn dairy heifers. Scientific Reports 2023; 13(1): 4672.
29. Mousavi S., Haghparast A., Mohammadi G., Tabatabaeizadeh SE. Prevalence of bovine leukemia virus (BLV) infection in the northeast of Iran. Veterinary Research Forum: An International Quarterly Journal 2014; 5(2): 135.
30. Murakami K., Kobayashi S., Konishi M., Kameyama KI., Tsutsui T. Nationwide survey of bovine leukemia virus infection among dairy and beef breeding cattle in Japan from 2009–2011. Journal of Veterinary Medical Science 2013; 75(8): 1123-1126.
31. Ohyashiki K., Ohyashiki JH., Iwama H., Hayashi S., Shay JW., Toyama K. Telomerase activity and cytogenetic changes in chronic myeloid leukemia with disease progression. Leukemia 1997; 11(2): 190-194.
32. Polat M., Takeshima SN., Aida Y. Epidemiology and genetic diversity of bovine leukemia virus. Virology Journal 2017; 14(1): 1-16.
33. Seeker LA., Holland R., Underwood S., et al. Method specific calibration corrects for DNA extraction method effects on relative telomere length measurements by quantitative PCR. PloS ONE 2016; 11(10): e0164046.
34. Seeker LA., Ilska, JJ., Psifid A., Wilbourn, RV., et al. Bovine telomere dynamics and the association between telomere length and productive lifespan. Scientific Reports 2018; 8(1): 12748.
35. Seeker LA., Underwood SL., Wilbourn RV., Dorrens J., et al. Telomere attrition rates are associated with weather conditions and predict productive lifespan in dairy cattle. Scientific Reports 2021; 11(1): 5589.
36. Selim A., Megahed AA., Kandeel S., Abdelhady A. Risk factor analysis of bovine leukemia virus infection in dairy cattle in Egypt. Comparative Immunology, Microbiology and Infectious Diseases 2020; 72: 101517.
37. Shay JW. Aging and cancer: are telomeres and telomerase the connection? Molecular Medicine Today 1995; 1(8): 378-384.
38. Sparling AM. An unusual presentation of enzootic bovine leukosis. Canadian Veterinary Journal 2000; 41(4): 315.
39. Suzuki H., Marushima K., Ohnishi Y., Horinouchi S. A novel pair of terminal protein and telomere-associated protein for replication of the linear chromosome of Streptomyces griseus IFO13350. Bioscience, Biotechnology and Biochemistry 2008; 72(11): 2973-2980.
40. Szczotka M., Kocki J., Iwan E., Pluta A. Determination of telomere length and telomerase activity in cattle infected with bovine leukaemia virus (BLV). Polish Journal of Veterinary Sciences 2019; 22(2): 391-403.
41. Szczotka M., Kuzmak J. Telomerase activity and telomere length in cattle ınfected with bovine leukemia virus (BLV). Journal of Comparative Pathology 2013; 1(148): 70.
42. Şevik M., Avcı O., İnce ÖB. An 8-year longitudinal sero-epidemiological study of bovine leukaemia virus (BLV) infection in dairy cattle in Turkey and analysis of risk factors associated with BLV seropositivity. Tropical Animal Health and Production 2015; 47(4): 715-720.
43. Şimşek A., Gürçay M., Parmaksız A., et al. Diyarbakır yöresindeki sığırların sindirim ve solunum sistemi problemlerinde enzootik bovine leukosis (EBL), bovine viral diare (BVD), infeksiyöz bovine rhinotracheitis (IBR) ve Mavi Dil (BT) enfeksiyonlarının rollerinin araştırılması. Dicle Üniversitesi Veteriner Fakültesi Dergisi 2017; 10(1): 13-18.
44. Tan MT., Yildirim Y., Erol N., Güngör AB. The seroprevalence of bovine herpes virus type 1 (BHV-1) and bovine leukemia virus (BLV) in selected dairy cattle herds in Aydin Province, Turkey. Turkish Journal of Veterinary and Animal Sciences 2006; 30(4): 353-357.
45. Tilesi F., Domenico EG., Pariset L., et al. Telomere length diversity in cattle breeds. Diversity 2010; 2(9): 1118-1129. Tözsér J. Comparative studies on retroviral proteases: Substrate specificity. Viruses 2010; 2(1): 147-165.
46. Trono KG., Pérez-Filgueira DM., Duffy S., Borca MV., Carrillo C. Seroprevalence of bovine leukemia virus in dairy cattle in Argentina: Comparison of sensitivity and specificity of different detection methods. Veterinary Microbiology 2001; 83(3): 235-248.
47. Uchida N., Olsuka T., Arima F., et al. Correlation of telomerase activity with development and progression of adult t-cell leukemia. Leukemia Research 1999; 23(3): 311-316.
48. Uysal A., Yilmaz H., Bilal T., et al. Seroprevalence of enzootic bovine leukosis in Trakya district (Marmara region) in Turkey. Preventive Veterinary Medicine 1998; 37(1-4): 121-128.
49. Watanuki S., Takeshima SN., Borjigin L., et al. Visualizing bovine leukemia virus (BLV)-infected cells and measuring BLV proviral loads in the milk of BLV seropositive dams. Veterinary Research 2019; 50(1): 102.
50. Weber AF., Meiske JC., Haggard DL., Sorensen DK., Domagala AM., Flaum AM. Failure to demonstrate transmission of enzootic bovine leukemia virus infection from cows to sheep by use of common injection needles. American Journal of Veterinary Research 1988; (49)11: 1814-1816.
51. Wu MC., Shanks RD., Lewin HA. Milk and fat production in dairy cattle influenced by advanced subclinical bovine leukemia virus infection. Proceedings of the National Academy of Sciences 1989; 86(3): 993-996.
52. Wu M., Zhu Y., Cong F., et al. Rapid detection of three rabbit pathogens by use of the Luminex x-TAG assay. BMC Veterinary Research 2018; 14(1): 1-6.
53. Yavru S., Kale M., Simsek A., Bulut O. Comparison of BLV antibodies in late pregnant and non-pregnant holstein cows using serum and milk elisa. Veterinarium 2007; 18(1): 50-55.
54. Yildirim Y., Yilmaz V., Otlu S., Şahin M. The seroprevalence of Bovine Leukemia Virus (BLV) infection in imported-breed cattle in Kars district in Turkey. Kafkas Universitesi Veteriner Fakultesi Dergisi 2008; 14(1): 99-103.
55. Yilmaz K., Gül Y., Özdemir H., Bolat Y. Investigations on the prevalence of enzootic bovine leucosis in cattle of Elaziǧ province and its vicinity. Turkish Journal of Veterinary & Animal Sciences 1997; 21(2): 115-123.
56. Yang Y., Fan W., Mao Y., et al. Bovine leukemia virus infection in cattle of China: Association with reduced milk production and increased somatic cell score. Journal of Dairy Science 2016; 99(5): 3688-3697.
57. Zhang N., Baker EC., Welsh TH., et al. Telomere dynamics in livestock. Biology 2023; 12(11): 1389.