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Lamivudine Inhibits the Replication of ALV-J Associated Acutely Transforming Virus and its Helper Virus and Tumor Growth In vitro and In vivo.

Wang Y, Xu S, Li S, Su H, Chang S, Li Y, Sun X, Zhao P, Cui Z - Front Microbiol (2015)

Bottom Line: To study the antiviral effects of lamivudine on avian leukosis virus subgroup J (ALV-J) and its inhibitory effect on the growth of fibrosarcomas caused by acute transforming avian leukosis virus, a series of experiments were performed in chicken embryo fibroblast cultures and 1-day-old chickens inoculated with an acutely transforming viral stock Fu-J (SDAU1005).Furthermore, the effect was dose dependent in the concentration range of 1-4 μg/ml.In chicken experiments, lamivudine could decrease the viral loads of SDAU1005 and Fu-J in the plasma of inoculated chickens, delay the appearance of acute sarcomas, and decrease chicken mortality in the early stage.

View Article: PubMed Central - PubMed

Affiliation: College of Animal Science and Veterinary Medicine, Shandong Agricultural University Tai'an, China.

ABSTRACT
To study the antiviral effects of lamivudine on avian leukosis virus subgroup J (ALV-J) and its inhibitory effect on the growth of fibrosarcomas caused by acute transforming avian leukosis virus, a series of experiments were performed in chicken embryo fibroblast cultures and 1-day-old chickens inoculated with an acutely transforming viral stock Fu-J (SDAU1005). This stock was prepared from an acutely fibrosarcoma of field cases in chicken farms and contained both the replication-defective virus Fu-J carrying v-fps oncogene and its helper virus ALV-J strain SDAU1005. The results from three different assays in cell cultures demonstrated the significant inhibitory effect of lamivudine on the replication of both SDAU1005 and Fu-J viruses. Furthermore, the effect was dose dependent in the concentration range of 1-4 μg/ml. In chicken experiments, lamivudine could decrease the viral loads of SDAU1005 and Fu-J in the plasma of inoculated chickens, delay the appearance of acute sarcomas, and decrease chicken mortality in the early stage. This model may be used to directly evaluate the inhibitory effects of lamivudine on such tumors and to understand the relationship between the replication-defective virus and its helper virus while also assessing tumor processes.

No MeSH data available.


Related in: MedlinePlus

Effect of lamivudine on Fu-J replication in chickens. (A) Growth of subcutaneous tumors induced by Fu-J virus in different groups. Administration of lamivudine delayed the tumor occurrence time and slowed down the speed of tumor growth at the early stage. (B) Survival plots of chickens infected with Fu-J virus intraperitoneally in different groups. Survival patterns of chickens in different groups showed a significant different from each other. (C) SDAU1005 plasma viral loads post-inoculation determined by real-time PCR demonstrated that Lamivudine could inhibit SDAU1005 replication in chickens. (D) Fu-J plasma viral loads post-inoculation determined by real-time PCR demonstrated that the replication of Fu-J virus was inhibited due to the reduction of SDAU1005. Differences in the expression level were assessed by Student’s t-tests. Differences were considered highly significant when p ≤ 0.01 (∗∗) and extremely significant p ≤ 0.001 (∗∗∗). The error bars represent the SEM. The data are representative of the results of three independent experiments.
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Figure 2: Effect of lamivudine on Fu-J replication in chickens. (A) Growth of subcutaneous tumors induced by Fu-J virus in different groups. Administration of lamivudine delayed the tumor occurrence time and slowed down the speed of tumor growth at the early stage. (B) Survival plots of chickens infected with Fu-J virus intraperitoneally in different groups. Survival patterns of chickens in different groups showed a significant different from each other. (C) SDAU1005 plasma viral loads post-inoculation determined by real-time PCR demonstrated that Lamivudine could inhibit SDAU1005 replication in chickens. (D) Fu-J plasma viral loads post-inoculation determined by real-time PCR demonstrated that the replication of Fu-J virus was inhibited due to the reduction of SDAU1005. Differences in the expression level were assessed by Student’s t-tests. Differences were considered highly significant when p ≤ 0.01 (∗∗) and extremely significant p ≤ 0.001 (∗∗∗). The error bars represent the SEM. The data are representative of the results of three independent experiments.

Mentions: To determine whether lamivudine had inhibitory effect on the growth of subcutaneous tumors induced by Fu-J, 80 1-day-old chickens were divided into four groups randomly and subcutaneously inoculated with the same dose of Fu-J. Chickens in groups 1, 2, and 3 were injected intramuscularly with 1, 2, and 4 mg lamivudine, respectively, for 7 days, while chickens in group 4 were inoculated with the same amount of PBS and served as a control group. The dynamic growth of subcutaneous tumors induced by Fu-J virus was investigated every day, and chickens were sacrificed when the tumors had grown to a certain extent. The results showed that subcutaneous tumors appeared approximately 5 days after inoculation and measured up to 4 cm in diameter at 15 days with malignant rapid growth (Figure 2A). However, subcutaneous tumors occurred later in chickens injected with lamivudine compared with those injected with PBS. Subcutaneous tumors could be detected after 6, 7, and 9 days after inoculation of chickens injected with 1, 2, and 4 mg lamivudine, respectively (Figure 2A). Moreover, the tumors grew slowly in chickens without lamivudine injection at an early stage, although tumors grew more rapidly at a later stage compared with those chickens without lamivudine injection. Therefore, it would appear that lamivudine has an inhibitory effect on the early growth of subcutaneous tumors but could not suppress virus replication or tumor growth completely.


Lamivudine Inhibits the Replication of ALV-J Associated Acutely Transforming Virus and its Helper Virus and Tumor Growth In vitro and In vivo.

Wang Y, Xu S, Li S, Su H, Chang S, Li Y, Sun X, Zhao P, Cui Z - Front Microbiol (2015)

Effect of lamivudine on Fu-J replication in chickens. (A) Growth of subcutaneous tumors induced by Fu-J virus in different groups. Administration of lamivudine delayed the tumor occurrence time and slowed down the speed of tumor growth at the early stage. (B) Survival plots of chickens infected with Fu-J virus intraperitoneally in different groups. Survival patterns of chickens in different groups showed a significant different from each other. (C) SDAU1005 plasma viral loads post-inoculation determined by real-time PCR demonstrated that Lamivudine could inhibit SDAU1005 replication in chickens. (D) Fu-J plasma viral loads post-inoculation determined by real-time PCR demonstrated that the replication of Fu-J virus was inhibited due to the reduction of SDAU1005. Differences in the expression level were assessed by Student’s t-tests. Differences were considered highly significant when p ≤ 0.01 (∗∗) and extremely significant p ≤ 0.001 (∗∗∗). The error bars represent the SEM. The data are representative of the results of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664723&req=5

Figure 2: Effect of lamivudine on Fu-J replication in chickens. (A) Growth of subcutaneous tumors induced by Fu-J virus in different groups. Administration of lamivudine delayed the tumor occurrence time and slowed down the speed of tumor growth at the early stage. (B) Survival plots of chickens infected with Fu-J virus intraperitoneally in different groups. Survival patterns of chickens in different groups showed a significant different from each other. (C) SDAU1005 plasma viral loads post-inoculation determined by real-time PCR demonstrated that Lamivudine could inhibit SDAU1005 replication in chickens. (D) Fu-J plasma viral loads post-inoculation determined by real-time PCR demonstrated that the replication of Fu-J virus was inhibited due to the reduction of SDAU1005. Differences in the expression level were assessed by Student’s t-tests. Differences were considered highly significant when p ≤ 0.01 (∗∗) and extremely significant p ≤ 0.001 (∗∗∗). The error bars represent the SEM. The data are representative of the results of three independent experiments.
Mentions: To determine whether lamivudine had inhibitory effect on the growth of subcutaneous tumors induced by Fu-J, 80 1-day-old chickens were divided into four groups randomly and subcutaneously inoculated with the same dose of Fu-J. Chickens in groups 1, 2, and 3 were injected intramuscularly with 1, 2, and 4 mg lamivudine, respectively, for 7 days, while chickens in group 4 were inoculated with the same amount of PBS and served as a control group. The dynamic growth of subcutaneous tumors induced by Fu-J virus was investigated every day, and chickens were sacrificed when the tumors had grown to a certain extent. The results showed that subcutaneous tumors appeared approximately 5 days after inoculation and measured up to 4 cm in diameter at 15 days with malignant rapid growth (Figure 2A). However, subcutaneous tumors occurred later in chickens injected with lamivudine compared with those injected with PBS. Subcutaneous tumors could be detected after 6, 7, and 9 days after inoculation of chickens injected with 1, 2, and 4 mg lamivudine, respectively (Figure 2A). Moreover, the tumors grew slowly in chickens without lamivudine injection at an early stage, although tumors grew more rapidly at a later stage compared with those chickens without lamivudine injection. Therefore, it would appear that lamivudine has an inhibitory effect on the early growth of subcutaneous tumors but could not suppress virus replication or tumor growth completely.

Bottom Line: To study the antiviral effects of lamivudine on avian leukosis virus subgroup J (ALV-J) and its inhibitory effect on the growth of fibrosarcomas caused by acute transforming avian leukosis virus, a series of experiments were performed in chicken embryo fibroblast cultures and 1-day-old chickens inoculated with an acutely transforming viral stock Fu-J (SDAU1005).Furthermore, the effect was dose dependent in the concentration range of 1-4 μg/ml.In chicken experiments, lamivudine could decrease the viral loads of SDAU1005 and Fu-J in the plasma of inoculated chickens, delay the appearance of acute sarcomas, and decrease chicken mortality in the early stage.

View Article: PubMed Central - PubMed

Affiliation: College of Animal Science and Veterinary Medicine, Shandong Agricultural University Tai'an, China.

ABSTRACT
To study the antiviral effects of lamivudine on avian leukosis virus subgroup J (ALV-J) and its inhibitory effect on the growth of fibrosarcomas caused by acute transforming avian leukosis virus, a series of experiments were performed in chicken embryo fibroblast cultures and 1-day-old chickens inoculated with an acutely transforming viral stock Fu-J (SDAU1005). This stock was prepared from an acutely fibrosarcoma of field cases in chicken farms and contained both the replication-defective virus Fu-J carrying v-fps oncogene and its helper virus ALV-J strain SDAU1005. The results from three different assays in cell cultures demonstrated the significant inhibitory effect of lamivudine on the replication of both SDAU1005 and Fu-J viruses. Furthermore, the effect was dose dependent in the concentration range of 1-4 μg/ml. In chicken experiments, lamivudine could decrease the viral loads of SDAU1005 and Fu-J in the plasma of inoculated chickens, delay the appearance of acute sarcomas, and decrease chicken mortality in the early stage. This model may be used to directly evaluate the inhibitory effects of lamivudine on such tumors and to understand the relationship between the replication-defective virus and its helper virus while also assessing tumor processes.

No MeSH data available.


Related in: MedlinePlus