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    控制 PRRS 病毒的新見解 New insights to control PRRS virus

    2021-06-17

    豬繁殖與呼吸綜合征(PRRS)病毒是目前養豬業面臨的最重要的病原之一。病毒的影響不單單是由疾病本身造成的,而是由于繼發感染的流行率增加。在管理和生物安全措施不能完全控制疾病的“問題”農場,免疫調節策略可以幫助控制PRRS。

    Porcine Reproductive and Respiratory Syndrome (PRRS) virus is one of the most important pathogens the swine industry is currently dealing with. The impact of the virus is not only caused by the disease itself, but is also due to increased prevalence of secondary infections. On “problem” farms, where farm management and biosecurity measures cannot fully control the disease, an immunomodulation strategy could help control PRRS.

    PRRS病毒(PRRSV)屬于動脈病毒科,是一種小的、有包膜的單股正鏈RNA病毒。PRRS的臨床癥狀變化很大。流產、死產胎、斷奶前死亡率和斷奶豬、育肥豬呼吸道疾病的大幅增加是PRRS常見的臨床癥狀。感染PRRSV的豬對繼發性細菌或病毒感染的敏感性顯著增加。例如,常見的豬鏈球菌并發感染。繼發感染的流行以及PRRSV造成的直接損失是這種病毒綜合征造成重大經濟影響的原因。豬肺泡巨噬細胞(PAMs)是PRRSV復制的主要靶細胞之一。這些細胞通過吞噬作用、抗原呈遞和產生細胞因子,充當抵御吸入微生物顆粒的第一道防線。PRRSV在豬肺泡巨噬細胞中復制時,這些基本功能直接受損。

    PRRS virus (PRRSV) belongs to the family of arterivirus_es and is a small, enveloped, positive single-stranded RNA virus. Clinical signs of PRRS are highly variable. Substantial increases in abortions, stillbirths, pre-weaning mortality and respiratory diseases in weaners and growers are commonly reported clinical signs of PRRS. The susceptibility of PRRSV-infected pigs to secondary bacte_rial or viral infections increases dramatically. For instance, concurrent infections with Streptococcus suis are frequently reported. The prevalence of secondary infections together with the direct losses caused by PRRSv are the reason for the major economic impact of this viral syndrome. One of the main target cells for PRRSV replication are porcine alveolar macrophages (PAMs). These cells serve as the first line of defence against inhaled microbial particles by means of phagocytosis, antigen presentation and production of cytokines. These basic functions are directly impaired when PRRSV replicates in PAMs.#p#分頁標題#e#

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    細胞因子失衡

    Imbalance between cytokines #p#分頁標題#e#

     

    更確切地說,促炎細胞因子的產生在PRRSV感染的動物中受到限制。缺乏足夠數量的促炎細胞因子似乎可以使PRRSV逃避宿主的免疫應答。因此,免疫系統未被激活,病毒清除也沒有啟動,使得PRRSV在宿主體內很容易繁殖。PRRSV的免疫抑制作用也可能增加繼發感染的風險。

    More specifically, the production of pro-inflammatory cytokines has shown to be limited in PRRSV-infected animals. The absence of sufficient amounts of pro-inflammato_ry cytokines seems to allow PRRSV to escape from the host immune response. Hence, the immune system is not acti_vated and viral clearance is not initiated, allowing PRRSV to multiply easily inside the host. The immunosuppressive effect of PRRSV may also contribute to the increased risk of secondary infections.

    除了先天性免疫系統對PRRSV感染的反應不足以及在促炎和抗炎細胞因子之間產生不平衡外,還有證據表明中和抗體和病毒特異性干擾素(IFN-γ)反應延遲。γ-干擾素參與抑制PRRSV復制,但在PRRSV感染的動物中下調。連同白細胞介素 10 (IL-10) 的上調,這可能導致巨噬細胞中CD163的增加,而CD163是PRRSV進入所需的受體復合物的組成部分。CD163的增加實際上促進了PRRSV進入和復制。由于PRRSV易受γ-干擾素的直接抗病毒作用影響,這似乎是免疫調節策略克服PRRS的一個有趣的靶點。

    Apart from the insufficient response of the innate immune system upon PRRSV infection and the creation of an imbalance between pro- and anti-inflammatory cytokines, there is also evidence that neutralising antibodies and virus-specific inter_feron-gamma (IFN-γ) responses are delayed. Interferon-gam_ma is involved in the inhibition of PRRSV replication but is downregulated in PRRSV-infected animals. Together with an upregulation of interleukin-10 (IL-10), this might cause an increase of CD163 in macrophages, which is a component of a complex of receptors required for PRRSV entry. An increase of CD163 actually promotes PRRSv entry and replication. As PRRSV is susceptible to the direct antiviral effect of IFN-γ, it seems an interesting target for immunomodulation strategies to overcome PRRS.#p#分頁標題#e#

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    調節炎癥反應

    Modulating the inflammatory response 

     

    近年來,#p#分頁標題#e#希特力 ®(α-單月桂酸甘油酯)因其調節炎癥反應的能力而備受關注。 大多數研究表明可以減少促炎細胞因子。 對于 PRRSV,需要下調白細胞介素10。另一方面,在PRRSV 感染期間應上調γ-干擾素。

     

    Lately,FRA C12 Dry(alpha-monolaurin) has been gaining more attention because of its ability to modulate the inflammatory response. Most research presents the reduction of pro-inflammatory cytokines. With respect to PRRSV, downregulation of IL-10 is desired. On the other hand, IFN-γ should be upregulated during PRRSV infection.

     

    #p#分頁標題#e#令人關注的是佰高威盛和比利時研究機構Poulpharm發現接種傳染性支氣管炎(IB)疫苗的肉雞使用 希特力 ® 后γ-干擾素顯著增加。此外,與對照組相比,使用希特力 ® 的肉雞抗IBV抗體滴度顯著增加。這些結果促使佰高威盛對 #p#分頁標題#e#希特力 ® 及其對PRRSV的影響進行更多的研究。

     

     

     

    Interestingly, Bioscwin/Fra and Belgian research facility Poulpharm discovered a significant increase of IFN-γ in broilers vaccinated against infectious bronchitis (IB) receiving FRA C12 Dry, a product based on glycerides of lauric acid, including alpha-monolaurin. Moreover, a significant increase in anti-IBV antibody titres was observed in broilers receiving the product compared to the control group. These results encouraged Bioscwin/Fra to conduct more research into the glyceride product and its effect on PRRSV.

     

    #p#分頁標題#e#在比利時一個 PRRSV 爆發的農場,   研究了使用        希特力 ® 的影響。 首先,一組母豬接受常規飼料并作為對照組。   第二組母豬在分娩前和哺乳期間使用了   希特力 ®, 斷奶仔豬也飼喂了該產品??偟膩碚f,與對照組相比,農民對使用 希特力 #p#分頁標題#e#® 組所取得的改善相當滿意。更具體地說,實驗組的仔豬斷奶前死亡率降低了29%,試驗組每頭母豬增加2.2頭斷奶仔豬,增長19.5%。

     

     

     

    At a farm suffering from a severe PRRSV outbreak in Belgium, the effects of the glyceride product were studied. Firstly, one group of sows received regular feed and served as a control group. The second group of sows received the glyceride product before farrowing and during lactation. The weaned piglets also received the product. In general, the farmer was quite satisfied with the improve_ments obtained in the group receiving the glycerides of C12 compared to the control group. More specifically, pre-weaning mortality was reduced by 29% in the treatment group. The number of weaned piglets in the treatment group increased by 2.2 piglets per sow, an increase of 19.5%.

    有趣的是,與實驗組相比,對照組的斷奶仔豬接受了更多針對關節問題的單獨注射(對照組3.2%:實驗組1.9%)。根據歷史數據,這些關節問題的起因很可能是豬鏈球菌。

    因此,#p#分頁標題#e#希特力 ® 似乎抑制了豬鏈球菌的繼發感染。

    Interestingly, weaned piglets in the control group received more individual injections against locomotor problems com_pared to the treatment group (3.2% versus 1.9% of the total amount of weaned piglets). Based on historical data the caus_ative agent of these locomotor problems was most likely S. suis. Hence, glycerides of C12 seemed to have suppressed the susceptibility to secondary infections with S. suis.

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    甘油酯和PRRSV的感染

    Glyceride and PRRSv shedding

     

    為了研究 希特力 ®#p#分頁標題#e# 對PRRSV感染的影響,Poulpharm研究小組收集了斷奶仔豬的唾液。在斷奶后7天和37天,隨機選擇10個圍欄,并提供咀嚼繩。仔豬被允許咀嚼繩子45分鐘,然后收集唾液進行分析。

     

     

    To study the effect of the glyceride product on PRRSV shed_ding, a Poulpharm research team collected oral fluids from weaned piglets. At seven and 37 days after weaning, ten pens were randomly selected and provided with chewing ropes. Piglets were allowed to chew the ropes for 45 minutes, after which oral fluids were collected for analysis.

    研究小組通過RT-qPCR試驗分析了仔豬唾液,臨界Ct值為42。42或更高的值被報告為陰性,而低于42的值反映了陽性結果,數值越低表明PRRSV濃度更高。

    The team analysed oral fluids by an RT-qPCR-test with a cut-off Ct-value of 42. Values of 42 and higher were reported as negative, whereas values below 42 reflected a positive result, with lower values indicating a higher PRRSV concentration.#p#分頁標題#e#

    斷奶后7天,對照組20%檢測出PRRSV陽性,而實驗組為10%。斷奶后37天,對照組70%呈陽性,實驗組只有20%?;谶@些結果,希特力 ® 減少了斷奶仔豬PRRSV感染的陽性率。

     

    At seven days after weaning, 20% of the pens in the control group tested positive for PRRSV, whereas in the treatment group this was 10%. At 37 days after weaning, 70% of the pens in the control group tested positive and only 20% in the treatment group. Based on these results, it seemed that FRA C12 Dry reduced PRRSV shedding in weaned piglets.圖片

    #p#分頁標題#e#1-斷奶后7天和37PRRSV陽性率
    Figure 1 - Percentage of PRRSV positive pens at seven and 37 days after weaning.

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    為了更好地了解希特力 #p#分頁標題#e#® 對PRRSV的作用方式,目前正在進行體外試驗。本試驗的目的是研究 希特力 ® 對PRRSV的直接抗病毒作用及其調節PRRSV感染細胞中多種細胞因子產生的能力。盡管目前還沒有完全了解其作用方式,希特力 ®#p#分頁標題#e# 是一種有前途的輔助手段,可直接或間接協助凈化PRRSV,并控制PRRSV陽性豬的繼發感染風險。

    To understand the mode of action of glycerides of C12 against PRRSV better, an in vitro test is currently being exe_cuted. The aim of this trial is to investigate the possible direct antiviral effect of glycerides of lauric acids against PRRSv and its ability to modulate the production of several cytokines in PRRSV-infected cells. Although the mode of action is currently not yet fully under_stood, glycerides of lauric acid seem to be an interesting and promising tool assisting directly and/or indirectly in the viral clearance of PRRSV and in controlling the risk of secondary infections in PRRSV-positive pigs. References are available on request.

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    希特力 #p#分頁標題#e#® 是控制PRRSV陽性豬繼發感染風險的有效手段

    Glycerides of lauric acid may be a tool for con_trolling the risk of secondary in_fections in PRRSV-positive pigs

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