Bluetongue virus transmission between ruminant host and Culicoides vectors: the importance of insect saliva proteins

蓝舌病病毒在反刍动物宿主和库蠓载体之间的传播：昆虫唾液蛋白的重要性

• 批准号: BB/F00852X/1
• 负责人: Peter Mertens
• 金额: $ 70.07万
• 依托单位: The Pirbright Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF00852X%2F1
• 关键词: Bluetongue; virus; transmission; between; ruminant

Bluetongue virus (BTV) is an arthropod-borne virus (an Arbovirus) transmitted between its ruminant hosts by blood feeding 'biting' midges (Culicoides spp.). The virus can infect most ruminants but causes haemorrhagic fever and severe clinical disease, in sheep (especially European breeds), some species of deer and to a lesser extent in cattle. Until a decade ago bluetongue was a disease of warm climates, areas containing populations of transmission-competent insect vector species. However, since 1998 BTV has moved progressively further north into Europe, a process related to warming of the local climate and an expanding distribution of certain midge vector populations. In 2006, a bluetongue outbreak occurred much further north than ever before, affecting Belgium, the Netherlands, Germany, Luxembourg, and North East France. The virus causes serve clinical disease in sheep and even cattle and approximately 50% of sheep and 10% of cattle developing clinical signs die. This outbreak confirms that some northern European midge species (which are the same as in the UK) can transmit BTV, and demonstrates that the whole of Europe, including the UK, is now under threat of further outbreaks. However, not all species of midge can transmit BTV efficiently, suggesting that transmission of the virus and the distribution of the disease is influenced by the insect vectors and the strain of virus involved. Blood feeding insects deposit saliva into the skin of the host. This causes inflammation and hypersensitivity in the skin, which results in the familiar red spots and itching, or even allergic vesicles, after midge or mosquito bites. BTV is transmitted in the insect's saliva and must survive the inflammation response in order to infect the ruminant host. However, the saliva also contains proteases (to help prevent clotting) which can modify the virus, even increasing its infectivity for the insect vector. It is often assumed that Arboviruses are injected into the blood of the host by feeding insects. However, midges use their mouthparts to cut and damage skin tissues, so they can feed on a mixed pool of blood, tissue and lymphatic fluid. BTV is not injected into blood vessels but left in the saliva deposited into the skin. The virus can replicate in certain skin cells and additionally in cells of the hosts inflammatory response that are attracted to the biting site. Therefore BTV may be present at higher levels in the skin than in the bloodstream, which may be important for uptake by feeding midges. So it appears that the virus has evolved to make use of the saliva proteins and the host's response, to increase the efficiency of transmission, and its chances of survival. We have recently developed methods to isolate midge saliva proteins in large quantities, to investigate their role in BTV transmission between vector insects and ruminant hosts. Initial studies indicate that different midge species have different saliva proteins, which may help explain differences in their vector 'competence'. There are unique facilities at Pirbright to work on midges, sheep and the bluetongue virus itself, that will allow us to explore their relationships and influence on transmission mechanisms. The project will compare saliva from different European, African and American midges, to determine the role of saliva proteins in BTV infection in mammalian and insect tissue culture cells, or in the sheep. The project will elucidate the importance of locally generated virus in the skin for BTV transmission and will also determine if the virus can be transmitted mechanically between infected and non-infected sheep (by other insects or by needle), or directly from one midge to another while they feed on the same sheep. The results of this research will improve our understanding of BTV transmission in Europe, helping to define the risk of bluetongue transmission and to implement appropriate control measures.

蓝舌病病毒（BTV）是一种节肢动物传播的病毒（虫媒病毒），在反刍动物宿主之间通过吸血“叮咬”蠓（库蠓属）传播。该病毒可感染大多数反刍动物，但在绵羊（特别是欧洲品种）、某些鹿种和牛中引起出血热和严重的临床疾病。直到十年前，蓝舌病还是一种温暖气候下的疾病，这些地区含有具有传播能力的昆虫媒介物种。然而，自1998年以来，BTV逐渐向北进入欧洲，这一过程与当地气候变暖和某些蚊媒种群分布扩大有关。2006年，蓝舌病爆发发生在比以往任何时候都更北的地方，影响了比利时、荷兰、德国、卢森堡和法国东北部。该病毒引起绵羊甚至牛的临床疾病，大约50%的绵羊和10%的牛出现临床症状死亡。这次爆发证实了一些北方欧洲的摇蚊物种（与英国相同）可以传播BTV，并表明包括英国在内的整个欧洲现在都面临进一步爆发的威胁。然而，并非所有种类的蠓都能有效地传播BTV，这表明病毒的传播和疾病的分布受到昆虫媒介和病毒株的影响。吸血昆虫将唾液存款到宿主的皮肤上。这会导致皮肤炎症和过敏，导致熟悉的红斑和瘙痒，甚至是过敏性小泡，在蚊虫叮咬后。BTV在昆虫的唾液中传播，并且必须在炎症反应中存活才能感染反刍动物宿主。然而，唾液也含有蛋白酶（以帮助防止凝血），可以修改病毒，甚至增加其对昆虫载体的感染性。通常认为虫媒病毒是通过取食昆虫而注入宿主血液的。然而，蠓用它们的口器切割和破坏皮肤组织，所以它们可以以血液，组织和淋巴液的混合池为食。BTV不会注射到血管中，而是留在沉积到皮肤中的唾液中。该病毒可以在某些皮肤细胞中复制，此外还可以在被吸引到叮咬部位的宿主炎症反应细胞中复制。因此，BTV在皮肤中的含量可能高于在血液中的含量，这对于吸浆虫的摄入可能很重要。因此，病毒似乎已经进化到利用唾液蛋白和宿主的反应，以提高传播效率和生存机会。我们最近开发了大量分离蠓唾液蛋白的方法，以研究它们在媒介昆虫和反刍动物宿主之间BTV传播中的作用。最初的研究表明，不同种类的吸浆虫有不同的唾液蛋白，这可能有助于解释它们的媒介“能力”的差异。在Pirbright有独特的设施来研究蠓、羊和蓝舌病病毒本身，这将使我们能够探索它们之间的关系和对传播机制的影响。该项目将比较来自不同欧洲、非洲和美洲的蠓的唾液，以确定唾液蛋白在哺乳动物和昆虫组织培养细胞或绵羊中BTV感染中的作用。该项目将阐明皮肤中局部产生的病毒对BTV传播的重要性，并将确定病毒是否可以在感染和未感染的绵羊之间机械传播（通过其他昆虫或针头），或直接从一只吸浆虫传播到另一只吸浆虫。这项研究的结果将提高我们对BTV在欧洲传播的理解，有助于确定蓝舌病传播的风险并实施适当的控制措施。

项目成果

Using shared needles for subcutaneous inoculation can transmit bluetongue virus mechanically between ruminant hosts

使用共用针头进行皮下接种可在反刍动物宿主之间机械传播蓝舌病病毒

• DOI: 10.5167/uzh-125307
• 发表时间: 2016
• 作者: Darpel, Karin E

Transplacental transmission of bluetongue virus 8 in cattle, UK.

• DOI: 10.3201/eid1512.090788
• 发表时间: 2009-12
• 期刊: Emerging infectious diseases
• 影响因子: 11.8
• 作者: Darpel KE;Batten CA;Veronesi E;Williamson S;Anderson P;Dennison M;Clifford S;Smith C;Philips L;Bidewell C;Bachanek-Bankowska K;Sanders A;Bin-Tarif A;Wilson AJ;Gubbins S;Mertens PP;Oura CA;Mellor PS
• 通讯作者: Mellor PS

Using shared needles for subcutaneous inoculation can transmit bluetongue virus mechanically between ruminant hosts.

• DOI: 10.1038/srep20627
• 发表时间: 2016-02-08
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Darpel KE;Barber J;Hope A;Wilson AJ;Gubbins S;Henstock M;Frost L;Batten C;Veronesi E;Moffat K;Carpenter S;Oura C;Mellor PS;Mertens PP
• 通讯作者: Mertens PP

Involvement of the skin during bluetongue virus infection and replication in the ruminant host.

• DOI: 10.1186/1297-9716-43-40
• 发表时间: 2012-04-30
• 期刊: Veterinary research
• 影响因子: 4.4
• 作者: Darpel KE;Monaghan P;Simpson J;Anthony SJ;Veronesi E;Brooks HW;Elliott H;Brownlie J;Takamatsu HH;Mellor PS;Mertens PP
• 通讯作者: Mertens PP

Clinical disease in sheep caused by bluetongue virus serotype 8, and prevention by an inactivated vaccine.

蓝舌病毒血清型 8 引起的绵羊临床疾病及灭活疫苗的预防。

• DOI: 10.1016/j.vaccine.2011.11.100
• 发表时间: 2012
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Moulin V