Analysis of Nucleotide Sequence of Tax, miRNA and LTR of Bovine Leukemia Virus in Cattle with Different Levels of Persistent Lymphocytosis in Russia
Abstract
:1. Introduction
2. Results
2.1. Selection of Cattle with High and Low Lymphocytosis
2.2. Variation among Tax Amino Acid Sequences
2.3. Identification of Single Nucleotide Polymorphisms in BLV miRNAs and Promoter Elements
2.4. Identification of SNPs in BLV LTR
2.5. An Association between BLV Sequence Variants and the Level of Persistent Lymphocytosis
3. Discussion
4. Materials and Methods
4.1. Sample Collection and Preparation
4.2. H3F3A Gene Quantitative Real-Time PCR Development
4.3. Quantification of BLV Provirus Copy Number
4.4. Amplification of LTR, pre-miRNA and Tax Gene Sequences
4.5. Sequence Data Analysis
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
References
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Variant Name | Position | Amino Acid | Domain | Respective Number of Cattle | Genotype |
---|---|---|---|---|---|
Tax_A | 40 | Q -> L | Zn finger domain | LE48 | 4 |
142 | V -> A | T-cell epitope | |||
233, 281 | L -> P, S -> P | -* | |||
Tax_B | 42 | E -> K | Zn finger domain | PL33 | 4 |
140 | N -> I | T-cell epitope | |||
142 | V -> A | T-cell epitope | |||
233, 281 | L -> P, S -> P | - | |||
Tax_C | 51 | E -> K | Zn finger domain | PL42 | 4 |
131 | I -> V | T-cell epitope | |||
186 | I -> V | CTL epitope & Leucine-rich domain | |||
69, 102, 214, 221, 228 | T -> M, V -> I, I -> T, T -> P, E -> A | - | |||
Tax_D | 52 | T -> I | Zn finger domain | PL20, PL30, PL32, PL44 | 4 |
183 | R -> K | CTL epitope & Leucine-rich domain | |||
278 | L -> I | B-cell epitope | |||
Tax_E | 52 | T -> I | Zn finger domain | PL13 | 4 |
140 | N -> K | T-cell epitope | |||
183 | R -> K | CTL epitope & Leucine-rich domain | |||
278 | L -> I | B-cell epitope | |||
69 | T -> M | - | |||
Tax_F | 52 | T -> I | Zn finger domain | PL35 | 4 |
124 | S -> F | T-cell epitope | |||
183 | R -> K | CTL epitope & Leucine-rich domain | |||
278 | L -> I | B-cell epitope | |||
2, 22, 73 | S -> A, N -> S, R -> Q | - | |||
Tax_G | 52 | T -> I | Zn finger domain | PL41 | 4 |
183 | R -> K | CTL epitope & Leucine-rich domain | |||
245 | A -> T | Multifunctional domain | |||
278 | L -> I | B-cell epitope | |||
235 | Q -> R | - | |||
Tax_H | 178 | F -> Y | CTL epitope & Leucine-rich domain | PL5 | 4 |
246 | I -> T | Multifunctional domain | |||
249 | F -> L | Multifunctional domain | |||
Tax_I | 245 | A -> T | Multifunctional domain | PL9 | 4 |
102, 214, 221 | V -> I, I -> T, T -> P | - | |||
Tax_J | 117 | Q -> R | T-cell epitope | PL45 | 4 |
102 | V -> I | - | |||
Tax_K | 141 | L -> S | T-cell epitope | PL40 | 4 |
186 | I -> V | CTL epitope & Leucine-rich domain | |||
Tax_L | 167 | T -> I | CTL epitope & Leucine-rich domain | PL14, PL15, PL21, PL25, PL27, PL28, PL36, PL39, PL46 | 7 |
173 | L -> P | CTL epitope & Leucine-rich domain | |||
257 | Y -> C | Multifunctional domain | |||
2, 69, 95, 214, 221, 233, 281 | S -> A5/9 §, T -> A, A -> T, I -> T8/9, T -> S, L -> P, S -> P | - | |||
Tax_M | 167 | T -> I | CTL epitope & Leucine-rich domain | PL38 | 7 |
173 | L -> P | CTL epitope & Leucine-rich domain | |||
198 | A -> T | CTL epitope | |||
257 | Y -> C | Multifunctional domain | |||
69, 95, 198, 214, 221, 227, 233, 281 | T -> A, A -> T, A -> T, I -> V, T -> S, S ->T, L -> P, S -> P | - | |||
Tax_N | 43 | R -> K | Zn finger domain | PL10 | 7 |
173 | L -> P | CTL epitope & Leucine-rich domain | |||
257 | Y -> C | Multifunctional domain | |||
2, 69, 95, 212, 221, 233, 281 | S -> A, T -> A, A -> T, V -> I, T -> S, L -> P, S -> P | - | |||
Tax_O | 102, 214, 221 | V -> I7/9, I -> T6/9, T -> P 6/9 | - | PL17, PL18, PL19, PL24, PL26, PL29, PL31, PL37, PL47 | 4 |
Variant Name | Position | Nucleotide | miRNAs | Respective Number of Cattle | Genotype |
---|---|---|---|---|---|
miRNA_A | 84, 171, 195, 210, 212 | A -> G, A -> G, G-> A, G-> A, T->A, | -Գ | PL8, PL14, PL15, PL25, PL28, PL36, PL38, PL39, PL46 | 7 |
310 | A -> del * | BLV-mir-B4-5p | |||
342 | G -> A | B4 pre-miRNA, putative A-box | |||
357 | A -> G | BLV-mir-B4-3p | |||
373, 392, 453 | G -> A, G -> A, C -> T | - | |||
462 | A -> G | BLV-mir-B5-5p | |||
497–498 | GA -> AG | BLV-mir-B5-3p | |||
miRNA_B | 168 | T -> del14/15 | - | AL2, AL3, PL11, PL17, PL23, PL24, PL26, PL29, PL31, PL37, PL40, PL41, PL42, PL45, PL47 | 4 |
miRNA_C | 106 | G -> A4/5 | - | PL5, PL12, PL33, PL43, LE48 | 4 |
154 | A -> G | BLV-mir-B2-3p | |||
miRNA_D | 249 | C -> G | BLV-mir-B3-5p, putative A-box | PL21, PL30, PL35, PL44 | 4 |
miRNA_E | 141 | G -> A | B2 pre-miRNA | PL9 | 4 |
168 | T -> del | - | |||
miRNA_F | 141 | G -> A | B2 pre-miRNA | PL18 | 4 |
168 | T -> del | - | |||
171 | A -> G | putativeA-box | |||
91, 300 | A -> G, A -> G | - | |||
miRNA_G | 64, 67, 84, 171, 195, 210, 212 | G -> A, A->T, A -> G, A -> G, G -> A, G -> A, T -> A | - | PL27 | 7 |
310 | A -> del | BLV-mir-B4-5p | |||
341 | C -> T | putative A-box | |||
342 | G -> A | B4 pre-miRNA, putative A-box | |||
357 | A -> G | BLV-mir-B4-3p | |||
373, 392, 453 | G -> A, G -> A, C -> T | - | |||
462 | A -> G | BLV-mir-B5-5p | |||
497–498 | GA -> AG | BLV-mir-B5-3p | |||
miRNA_H | 97, 168 | A -> G, T -> del | - | PL16 | 4 |
420 | A -> G | putative B-box | |||
miRNA_I | 168 | T -> del | - | PL19 | 4 |
420 | A -> G | putative B-box | |||
467 | A -> G | BLV-mir-B5-5p, putative B-box | |||
miRNA_J | 107 | A -> G | - | PL20 | 4 |
239 | C -> T | BLV-mir-B3-5p | |||
249 | C -> G | BLV-mir-B3-5p, putative A-box | |||
miRNA_K | 181 | G ->A | putative B-box | PL32 | 4 |
249 | C -> G | BLV-mir-B3-5p, putative A-box |
Variant Name | Position | Nucleotide | Regulatory Element | Respective Number of Cattle | Genotype |
---|---|---|---|---|---|
LTR_A | −133 | G -> A | TRE2 | PL12, PL22, PL33, LE48 | 4 |
+5 | C -> T | putative GR & PR site | |||
+183 | C -> T | DAS | |||
LTR_B | −133 | G -> A | TRE2 | PL43 | 4 |
+5 | C -> T | putative GR & PR site | |||
+150 | A -> C | Box A (DAS) | |||
+183 | C -> T | DAS | |||
+185 | C -> T | Box C (DAS) | |||
LTR_C | +187 | C -> A | Box C (DAS) | AL1, AL2, PL23, PL26, PL31, PL37, PL45 | 4 |
LTR_D | −4 | A -> G | CAP site | PL11, PL17, PL19, PL24, PL42 | 4 |
+187 | C -> A | Box C (DAS) | |||
LTR_E | −4 | A -> G | CAP site | PL9, PL18 | 4 |
+5 | C -> T | putative GR & PR site | |||
+187 | C -> A | Box C (DAS) | |||
LTR_F | +161 | T -> C | DAS | PL13, PL20, PL30, PL32, PL44 | 4 |
LTR_G | −10 | A -> G | CAP site | PL35 | 4 |
+161 | T -> C | DAS | |||
+190 | T -> C | Box C (DAS) | |||
LTR_H | the consensus sequence-like | PL41 | 4 | ||
LTR_I | −65 | T -> C | GRE | PL5 | 4 |
LTR_J | −142 | G -> A | NF-kB-like protein | PL4 | 4 |
−11 | T -> C | CAP site | |||
LTR_K | −122 | T -> A | E box 2 | PL29, PL40, PL47 | 4 |
LTR_L | −133 | G -> C | TRE2 | PL14, PL15, PL25, PL27, PL28, PL36, PL38, PL39, PL46 | 7 |
+11 | C -> T | putative Sp1 & GR site | |||
+150 | A -> G | Box A (DAS) | |||
+160 | C -> T | DAS | |||
LTR_M | +11 | C -> T | putative Sp1 & GR site | PL10 | 7 |
+150 | A -> G | Box A (DAS) |
Gene/Region | Variant | Mutation | Regulatory Domains/Elements |
---|---|---|---|
Tax | Tax H | F(178)Y I(246)T, F(249)L | CTL epitope & Leucine-rich domain Multifunctional domain |
Tax I | - | - | |
Tax N | R(43)K V(212)I | Zn finger domain adjacent to CTL epitope | |
Tax E | - | - | |
miRNA | miRNA_E | G(141)A | B2 pre-miRNA |
miRNA_H | A(420)H | putative B-box | |
miRNA_F | G(141)A | B2 pre-miRNA | |
miRNA_I | A(420)H A(467)G | putative B-box BLV-mir-B5-5p & putative B-box | |
miRNA_J | C(239)T | BLV-mir-B3-5p | |
LTR | LTR_J | G(−142)A T(−11)C | NF-kB-like protein CAP site |
LTR_I | T(−65)C | GRE | |
LTR_M | - | - | |
LTR_E | A(−4)G | CAP site | |
LTR_D | A(−4)G | CAP site |
Gene/Region | Variant | Mutation | Regulatory Domains/Elements |
---|---|---|---|
Tax | Tax O | - | - |
Tax L | - | - | |
Tax B | E(42)K, V(142)A | Zn finger domain, T-cell epitope | |
Tax M | A(198)T | CD8+ T-cell epitope | |
Tax G | - | - | |
Tax C | E(51)K, I(131)V | Zn finger domain, T-cell epitope | |
Tax J | Q(117)R | T-cell epitope | |
miRNA | miRNA_K | C(249)G G(181)A | BLV-mir-B3-5p, putative B-box |
miRNA_A | A(310)del *, G(342)A, A(357)G, A(462)G, GA(497–498)AG | BLV-mir-B4-5p, B4 pre-miRNA with putative A-box, BLV-mir-B4-3p, BLV-mir-B5-5p, BLV-mir-B5-3p | |
miRNA_B | - | - | |
miRNA_D | C(249)G | BLV-mir-B3-5p | |
miRNA_C | A(154)G | BLV-mir-B2-3p | |
LTR | LTR F | - | - |
LTR L | G(−133)C, C(+160)T | CRE2, DAS | |
LTR A | G(−133)A, C(+183)T | CRE2, DAS | |
LTR K | T(−122)A | E box2 | |
LTR H | - | - | |
LTR C | - | - | |
LTR B | G(−133)A, A(+150)C, C(+183)T, C(+185)T | CRE2, Box A (DAS), DAS, Box C (DAS) |
Region | Predominant Residue (Position) | Chi-Square p-Value | |
---|---|---|---|
Low PL (Group I) | High PL (Group II) | ||
Tax | I(214) | T(214) | 0.11416 |
T(221) | S(221) | 0.34776 | |
L(233) | P(233) | 0.35330 | |
S(281) | P(281) | 0.35331 | |
miRNA | del(168) | T(168) | 0.13392 |
A(441) | G(441) | 0.11976 | |
LTR | A(+187) | C(+187) | 0.00737 * |
Cattle # | Lymphocyte × 103/µL | WBC × 103/µL | Clinical Stage | Breed | Herd # | Proviral Copy Number per 103 Cells |
---|---|---|---|---|---|---|
AL1 | 8.8 | 14 | AL | B-a-W | I | 0.01 |
AL2 | 7.6 | 11 | AL | B-a-W | I | 224.8 |
AL3 | 9.2 | 14 | AL | B-a-W | I | 0.7 |
PL4 | 11.2 | 16 | PL | B-a-W | I | 1.1 |
PL5 | 12.8 | 17 | PL | RedStep | II | 52.4 |
PL6 | 12.2 | 17 | PL | B-a-W | I | 0.01 |
PL7 | 11.9 | 17 | PL | Ayrshire | III | 0.1 |
PL8 | 12.4 | 17.5 | PL | RedStep | II | 0.3 |
PL9 | 14.4 | 17.5 | PL | B-a-W | IV | 0.4 |
PL10 | 10.6 | 18 | PL | RedStep | II | 1.1 |
PL11 | 11.7 | 18 | PL | B-a-W | IV | 1.3 |
PL12 | 9.4 | 18 | PL | B-a-W | IV | 1.8 |
PL13 | 10.3 | 18 | PL | Ayrshire | III | 3.9 |
PL14 | 12.2 | 18 | PL | Ayrshire | III | 8.4 |
PL15 | 12.6 | 18.3 | PL | Ayrshire | III | 16.0 |
PL16 | 14.3 | 18.3 | PL | B-a-W | IV | 23.6 |
PL17 | 11.5 | 18.3 | PL | B-a-W | IV | 50.7 |
PL18 | 14.1 | 18.5 | PL | B-a-W | IV | 76.1 |
PL19 | 12.0 | 18.5 | PL | B-a-W | IV | 90.8 |
PL20 | 12.0 | 19 | PL | RedStep | II | 96.6 |
PL21 | 14.3 | 19 | PL | Ayrshire | III | 112.6 |
PL22 | 13.1 | 19 | PL | B-a-W | IV | 150.8 |
PL23 | 13.3 | 19.5 | PL | B-a-W | IV | 159.1 |
PL24 | 18.3 | 19.5 | PL | B-a-W | IV | 160.1 |
PL25 | 9.0 | 19.5 | PL | Ayrshire | III | 226.7 |
PL26 | 13.4 | 20 | PL | B-a-W | IV | 271.3 |
PL27 | 11.4 | 20 | PL | Ayrshire | III | 300.0 |
PL28 | 13.6 | 20 | PL | RedStep | II | 330.2 |
PL29 | 14.3 | 21 | PL | Ayrshire | III | 41.6 |
PL30 | 12.2 | 21 | PL | Ayrshire | III | 51.1 |
PL31 | 14.9 | 21 | PL | B-a-W | I | 5.3 |
PL32 | 18.0 | 22 | PL | RedStep | II | 266.2 |
PL33 | 15.0 | 25 | PL | B-a-W | IV | 235.2 |
PL34 | 16.2 | 24.6 | PL | B-a-W | IV | 314.6 |
PL35 | 19.2 | 26 | PL | RedStep | II | 35.2 |
PL36 | 16.5 | 28.5 | PL | Ayrshire | III | 44.9 |
PL37 | 22.3 | 29 | PL | B-a-W | I | 312.3 |
PL38 | 23.3 | 31 | PL | Ayrshire | III | 201.2 |
PL39 | 27.2 | 32 | PL | RedStep | II | 228.4 |
PL40 | 27.5 | 34 | PL | RedStep | II | 62.9 |
PL41 | 27.2 | 34 | PL | B-a-W | I | 359.9 |
PL42 | 25.6 | 35 | PL | B-a-W | IV | 109.4 |
PL43 | 25.6 | 35 | PL | B-a-W | IV | 222.4 |
PL44 | 21.6 | 36 | PL | Ayrshire | III | 182.8 |
PL45 | 27.7 | 36 | PL | B-a-W | IV | 217.1 |
PL46 | 30.0 | 38 | PL | Ayrshire | III | 143.6 |
PL47 | 34.0 | 42 | PL | RedStep | II | 284.4 |
LE48 | 44.8 | 56 | LE | B-a-W | IV | 175.0 |
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Pluta, A.; Blazhko, N.V.; Ngirande, C.; Joris, T.; Willems, L.; Kuźmak, J. Analysis of Nucleotide Sequence of Tax, miRNA and LTR of Bovine Leukemia Virus in Cattle with Different Levels of Persistent Lymphocytosis in Russia. Pathogens 2021, 10, 246. https://doi.org/10.3390/pathogens10020246
Pluta A, Blazhko NV, Ngirande C, Joris T, Willems L, Kuźmak J. Analysis of Nucleotide Sequence of Tax, miRNA and LTR of Bovine Leukemia Virus in Cattle with Different Levels of Persistent Lymphocytosis in Russia. Pathogens. 2021; 10(2):246. https://doi.org/10.3390/pathogens10020246
Chicago/Turabian StylePluta, Aneta, Natalia V. Blazhko, Charity Ngirande, Thomas Joris, Luc Willems, and Jacek Kuźmak. 2021. "Analysis of Nucleotide Sequence of Tax, miRNA and LTR of Bovine Leukemia Virus in Cattle with Different Levels of Persistent Lymphocytosis in Russia" Pathogens 10, no. 2: 246. https://doi.org/10.3390/pathogens10020246