Microbial translocation is a cause of systemic immune activation in HIV/SIV infection. In the present study, we found a lower CD8+ T cell activation level in Macaca leonina (northern pig-tailed macaques, NPMs) than in...Microbial translocation is a cause of systemic immune activation in HIV/SIV infection. In the present study, we found a lower CD8+ T cell activation level in Macaca leonina (northern pig-tailed macaques, NPMs) than in Macaca mulatta (Chinese rhesus macaques, ChRMs) during SIVmac239 infection. Furthermore, the levels of plasma LPS-binding protein and soluble CD14 in NPMs were lower than those in ChRMs. Compared with ChRMs, SIV-infected NPMs had lower Chiu scores, representing relatively normal intestinal mucosa. In addition, no obvious damage to the ileum or colon epithelial barrier was observed in either infected or uninfected NPMs, which differed to that found in ChRMs. Furthermore, no significant microbial translocation (Escherichia coli) was detected in the colon or ileum of infected or uninfected NPMs, which again differed to that observed in ChRMs. In conclusion, NPMs retained superior intestinal integrity and limited microbial translocation during SIV infection, which may contribute to their lower immune activation compared with ChRMs.展开更多
The northem pig-tailed macaque (NPM, Macaca leonina) has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3...The northem pig-tailed macaque (NPM, Macaca leonina) has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3-11 year old captive northem pig-tailed macaques using HITACHI 7600-20 automated chemistry analyzer in order to determine the influences of age and gender on these items. The results showed that serum IgA, IgM, C3 and C4 levels were not correlated with age (P〉0.05), while serum IgG levels increased progressively with age (r=0.202; P=0.045). Serum IgG, IgA, IgM and C3 levels were higher in females than in males (P〈0.05). Moreover, serum C3 concentration was both positively and strongly correlated with that of C4 (r=0.700; P〈0.0001). This study provides basic serum immunoglobulin and complement data of captive northem pig-tailed macaques, which may prove useful for future breeding efforts and biomedical research.展开更多
Pig-tailed macaques(Macaca nemistrina group) have been extensively used as non-human primate animal models for various human diseases in recent years, notably for AIDS research due to their sensitivity to HIV-1. North...Pig-tailed macaques(Macaca nemistrina group) have been extensively used as non-human primate animal models for various human diseases in recent years, notably for AIDS research due to their sensitivity to HIV-1. Northern pig-tailed macaques(M. leonina) are distributed in China and other surrounding Southeast Asia countries. Although northern pig-tailed macaques have been bred on a large scale as experimental animals since 2012, the reference value of normal levels of leukocytes is not available. To obtain such information, 62 blood samples from male and female healthy northern pig-tailed macaques at different ages were collected. The normal range of major leukocyte subpopulations, such as T lymphocytes, B lymphocytes, natural killer(NK) cells, monocytes, and the expression levels of activation or differentiation related molecules(CD38, HLA-DR, CCR5, CD21, IgD, CD80 and CD86) on lymphocytes were analyzed by flow cytometry. The counts of B cells decreased with age, but those of CD8+ T cells and NK cells and the frequency of CD38+HLA-DR+CD4+ T cells were positively correlated with age. The counts of leukocyte subpopulations were higher in males than those in females except for CD4+ T cells. Males also showed higher expression levels of Ig D and CD21 within B cells. This study provides basic data about the leukocyte subpopulations of northern pig-tailed macaques and compares this species with commonly used Chinese rhesus macaques(M. mulatta), which is meaningful for the biomedical application of northern pig-tailed macaques.展开更多
Northern pig-tailed macaques (NPMs, Macaca leonina) are susceptible to HIV-1 infection largely due to the loss of HIV-l-restricting factor TRIM5a. However, great impediments still exist in the persistent replication...Northern pig-tailed macaques (NPMs, Macaca leonina) are susceptible to HIV-1 infection largely due to the loss of HIV-l-restricting factor TRIM5a. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences (CDSs) showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection.展开更多
Viral reservoirs of HIV-1 are a major obstacle for curing AIDS. The novel animal models that can be directly infected with HIV-I will contribute to develop effective strategies for eradicating infections. Here, we ino...Viral reservoirs of HIV-1 are a major obstacle for curing AIDS. The novel animal models that can be directly infected with HIV-I will contribute to develop effective strategies for eradicating infections. Here, we inoculated 4 northern pig-tailed macaques (NPM) with the HIV-1 strain HIV-1NL4.3 and moni- tored the infection for approximately 3 years (150 weeks). The HIV-l-infected NPMs showed transient viremia for about 10 weeks after infection. However, cell-associated proviral DNA and viral RNA persisted in the peripheral blood and lymphoid organs for about 3 years. Moreover, replication-competent HIV-1 could be successfully recovered from peripheral blood mononuclear cells (PBMCs) during long-term infection. The numbers of resting CD4~ T cells in HIV-1 infected NPMs harboring proviruses fell within a range of 2- to 3-1oglo per million cells, and these proviruses could be reactivated both ex vivo and in vivo in response to co-stimulation with the latency-reversing agents JQ1 and prostratin. Our results suggested that NPMs can be infected with HIV-1 and a long-term viral reservoir was formed in NPMs, which might serve as a potential model for HIV-1 reservoir research.展开更多
The northern pig-tailed macaque (Macaca leonina) has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus...The northern pig-tailed macaque (Macaca leonina) has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus type 1 (HIV-1), which may be due to the absence of a TRIM5 protein restricting HIV-1 replication. Here we investigated the infection potentials of six laboratory adapted HIV-1 strains and three primary HIV-1 isolates in PBMCs from M. leonina. The results indicate that these strains are characterized by various but low replication levels, and among which, HIV-INL4-3 shows the highest replication ability. Based on the abundant evidence of species-specific interactions between restriction factors APOBEC3 and HIV/SIV-derived Vif protein, we subsequently examined the replication potentials of v/f-substituted HIV-1 (HSIV) in M. leonina PBMCs. Notably, HSIV-vifmac and stHIV-lsv chimeras, two HIV-1Ni.4-3-derived viruses encoding the viral infectivity factor (Vif) protein from SIVmac239, replicated robustly in cells from M. leonina, which suggests that HSIV could effectively antagonize the antiviral activity of APOBEC3 proteins expressed in cells of M. leonina. Therefore, our data demonstrate that M. leonina has the potential to be developed into a promising animal model for human AIDS.展开更多
在利用视频监控技术对群养猪只进行自动行为监测时,对猪只准确定位并辨别其头尾位置对提高监测水平至关重要,基于此提出一种基于YOLO v3(You only look once v3)模型与图结构模型(Pictorial structure models)的猪只头尾辨别方法。首先...在利用视频监控技术对群养猪只进行自动行为监测时,对猪只准确定位并辨别其头尾位置对提高监测水平至关重要,基于此提出一种基于YOLO v3(You only look once v3)模型与图结构模型(Pictorial structure models)的猪只头尾辨别方法。首先,利用基于深度卷积神经网络的YOLO v3目标检测模型,训练猪只整体及其头部和尾部3类目标的检测器,从而在输入图像中获得猪只整体及头尾部所有的检测结果;然后,引入图结构模型,描述猪只的头尾结构特征,对每个猪只整体检测矩形框内的头尾部位组合计算匹配得分,选择最优的部位组合方式;对部分部位漏检的情况,采取阈值分割与前景椭圆拟合的方法,根据椭圆长轴推理出缺失部位。在实际猪场环境下,通过俯拍获得猪舍监控视频,建立了图像数据集,并进行了检测实验。实验结果表明,与直接利用YOLO v3模型相比,本文方法对头尾定位的精确率和召回率均有一定提高。本文方法对猪只头尾辨别精确率达到96.22%,与其他方法相比具有明显优势。展开更多
基金partly supported by grants from the National Natural Science Foundation of China(U1802284 81471620,81671627,81771770,81571606)+1 种基金13th Five-Year Key Scientific and Technological Program of China(2017ZX10304402-002-004,2017ZX10202102-001-005,2018ZX10301101-002-003,2018ZX10301406-003)Knowledge Innovation Program of the Chinese Academy of Sciences(ZDRW-ZS-2016-4)
文摘Microbial translocation is a cause of systemic immune activation in HIV/SIV infection. In the present study, we found a lower CD8+ T cell activation level in Macaca leonina (northern pig-tailed macaques, NPMs) than in Macaca mulatta (Chinese rhesus macaques, ChRMs) during SIVmac239 infection. Furthermore, the levels of plasma LPS-binding protein and soluble CD14 in NPMs were lower than those in ChRMs. Compared with ChRMs, SIV-infected NPMs had lower Chiu scores, representing relatively normal intestinal mucosa. In addition, no obvious damage to the ileum or colon epithelial barrier was observed in either infected or uninfected NPMs, which differed to that found in ChRMs. Furthermore, no significant microbial translocation (Escherichia coli) was detected in the colon or ileum of infected or uninfected NPMs, which again differed to that observed in ChRMs. In conclusion, NPMs retained superior intestinal integrity and limited microbial translocation during SIV infection, which may contribute to their lower immune activation compared with ChRMs.
基金Foundation items: This work was supported by the National Natural Science Foundation of China (81172876, U0832601, 81273251, U1202228) the National Special Science Research Program of China (2012CBA01305) the National Science and Technology Major Project (2013ZX10001-002, 2012ZX10001-007) and the Knowledge Innovation Program of CAS (KSCX2-EW-R-13).
文摘The northem pig-tailed macaque (NPM, Macaca leonina) has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3-11 year old captive northem pig-tailed macaques using HITACHI 7600-20 automated chemistry analyzer in order to determine the influences of age and gender on these items. The results showed that serum IgA, IgM, C3 and C4 levels were not correlated with age (P〉0.05), while serum IgG levels increased progressively with age (r=0.202; P=0.045). Serum IgG, IgA, IgM and C3 levels were higher in females than in males (P〈0.05). Moreover, serum C3 concentration was both positively and strongly correlated with that of C4 (r=0.700; P〈0.0001). This study provides basic serum immunoglobulin and complement data of captive northem pig-tailed macaques, which may prove useful for future breeding efforts and biomedical research.
基金This work was supported by the National Special Science Research Program of China (2012CBA01305) the National Natural Science Foundation of China (81172876, U0832601, 81273251, U1202228) the Knowledge Innovation Program of CAS (KSCX2-EW-R-13) and the National Science and Technology Major Project (2013ZX10001-002, 2012ZX10001-007)We thank Mr. Zhen-Fei Hu,Gui Li and Dong-Ti Huang of Kunming Primate Research Center for their assistance with the experiments.
文摘Pig-tailed macaques(Macaca nemistrina group) have been extensively used as non-human primate animal models for various human diseases in recent years, notably for AIDS research due to their sensitivity to HIV-1. Northern pig-tailed macaques(M. leonina) are distributed in China and other surrounding Southeast Asia countries. Although northern pig-tailed macaques have been bred on a large scale as experimental animals since 2012, the reference value of normal levels of leukocytes is not available. To obtain such information, 62 blood samples from male and female healthy northern pig-tailed macaques at different ages were collected. The normal range of major leukocyte subpopulations, such as T lymphocytes, B lymphocytes, natural killer(NK) cells, monocytes, and the expression levels of activation or differentiation related molecules(CD38, HLA-DR, CCR5, CD21, IgD, CD80 and CD86) on lymphocytes were analyzed by flow cytometry. The counts of B cells decreased with age, but those of CD8+ T cells and NK cells and the frequency of CD38+HLA-DR+CD4+ T cells were positively correlated with age. The counts of leukocyte subpopulations were higher in males than those in females except for CD4+ T cells. Males also showed higher expression levels of Ig D and CD21 within B cells. This study provides basic data about the leukocyte subpopulations of northern pig-tailed macaques and compares this species with commonly used Chinese rhesus macaques(M. mulatta), which is meaningful for the biomedical application of northern pig-tailed macaques.
基金supported by the National Special Science Research Program of China(2012CBA01305)National Natural Science Foundation of China(81172876+6 种基金814716208127325181571606U0832601)National Science and Technology Major Project(2014ZX10005-002-006)Knowledge Innovation Program of CAS(KJZD-EW-L10-02)Yunnan Applicative and Basic Research Program(2014FB181)
文摘Northern pig-tailed macaques (NPMs, Macaca leonina) are susceptible to HIV-1 infection largely due to the loss of HIV-l-restricting factor TRIM5a. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences (CDSs) showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection.
基金supported by the National Basic Research Program of China (2012CBA01305)the National Natural Science Foundation of China (81172876+11 种基金 81571606 81471620 U0832601 30671960)the 13th Five-Year Key Scientific and Technological Program of China (2017ZX10304402002-004 2017ZX10202102-001-005)the Knowledge Innovation Program of the Chinese Academy of Sciences (KSCX2-EW-R-13 KJZD-EW-L10-02 CASIMM0320163020)the National Key Research & Development Plan (2016YFC1201000)Yunnan Applicative and Basic Research Program (2014FB181 201501PH00015)
文摘Viral reservoirs of HIV-1 are a major obstacle for curing AIDS. The novel animal models that can be directly infected with HIV-I will contribute to develop effective strategies for eradicating infections. Here, we inoculated 4 northern pig-tailed macaques (NPM) with the HIV-1 strain HIV-1NL4.3 and moni- tored the infection for approximately 3 years (150 weeks). The HIV-l-infected NPMs showed transient viremia for about 10 weeks after infection. However, cell-associated proviral DNA and viral RNA persisted in the peripheral blood and lymphoid organs for about 3 years. Moreover, replication-competent HIV-1 could be successfully recovered from peripheral blood mononuclear cells (PBMCs) during long-term infection. The numbers of resting CD4~ T cells in HIV-1 infected NPMs harboring proviruses fell within a range of 2- to 3-1oglo per million cells, and these proviruses could be reactivated both ex vivo and in vivo in response to co-stimulation with the latency-reversing agents JQ1 and prostratin. Our results suggested that NPMs can be infected with HIV-1 and a long-term viral reservoir was formed in NPMs, which might serve as a potential model for HIV-1 reservoir research.
基金Foundation items: This work was supported by the National Basic Research Program (2012CBA01305) the National Natural Science Foundation of China (81172876, U0832601, 81273251 and U 1202228) the Knowledge Innovation Program of CAS (KSCX2-EW-R-13, Y206A- 71181), and the Key Scientific and Technological Program of China (2012ZX10001-007, 2013ZX10001-002). Acknowledgements: We thank Prof. Guang-Xia GAO (Institute of Biophysics, Chinese Academy of Sciences) for kindly providing HSIV proviral plasmids.We also thank Long-Bao LV, Gui LI and Dong- Ti HUANG of Kunming Primate Research Center for their assistance in obtaining blood samples from northem pig-tailed macaques (M. leonina) and Chinese rhesus macaques.
文摘The northern pig-tailed macaque (Macaca leonina) has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus type 1 (HIV-1), which may be due to the absence of a TRIM5 protein restricting HIV-1 replication. Here we investigated the infection potentials of six laboratory adapted HIV-1 strains and three primary HIV-1 isolates in PBMCs from M. leonina. The results indicate that these strains are characterized by various but low replication levels, and among which, HIV-INL4-3 shows the highest replication ability. Based on the abundant evidence of species-specific interactions between restriction factors APOBEC3 and HIV/SIV-derived Vif protein, we subsequently examined the replication potentials of v/f-substituted HIV-1 (HSIV) in M. leonina PBMCs. Notably, HSIV-vifmac and stHIV-lsv chimeras, two HIV-1Ni.4-3-derived viruses encoding the viral infectivity factor (Vif) protein from SIVmac239, replicated robustly in cells from M. leonina, which suggests that HSIV could effectively antagonize the antiviral activity of APOBEC3 proteins expressed in cells of M. leonina. Therefore, our data demonstrate that M. leonina has the potential to be developed into a promising animal model for human AIDS.
文摘在利用视频监控技术对群养猪只进行自动行为监测时,对猪只准确定位并辨别其头尾位置对提高监测水平至关重要,基于此提出一种基于YOLO v3(You only look once v3)模型与图结构模型(Pictorial structure models)的猪只头尾辨别方法。首先,利用基于深度卷积神经网络的YOLO v3目标检测模型,训练猪只整体及其头部和尾部3类目标的检测器,从而在输入图像中获得猪只整体及头尾部所有的检测结果;然后,引入图结构模型,描述猪只的头尾结构特征,对每个猪只整体检测矩形框内的头尾部位组合计算匹配得分,选择最优的部位组合方式;对部分部位漏检的情况,采取阈值分割与前景椭圆拟合的方法,根据椭圆长轴推理出缺失部位。在实际猪场环境下,通过俯拍获得猪舍监控视频,建立了图像数据集,并进行了检测实验。实验结果表明,与直接利用YOLO v3模型相比,本文方法对头尾定位的精确率和召回率均有一定提高。本文方法对猪只头尾辨别精确率达到96.22%,与其他方法相比具有明显优势。