禽类动物病毒

PART 1: 禽流感病毒（Avian influenza virus，AIV）

禽流感，其实就是禽类的病毒性流行性感冒。低致病性流感病毒感染后可以表现为轻度的呼吸道症状、消化道症状，死亡率较低；高致病性流感病毒感染则表现为较严重的全身性、出血性、败血性症状，死亡率较高。

Avian influenza, is, in fact avian viral influenza. Low pathogenic influenza virus infection can be manifested as mild respiratory symptoms, gastrointestinal symptoms, and low mortality; infection with highly pathogenic influenza virus can produce more severe systemic, hemorrhagic and septic symptoms, and the mortality rate is higher.

流感病基因组为8个分节段的RNA，这让它在自我复制的过程中极易发生变异，常会导致病毒免疫原性和抗原性的改变，使得不能轻易感染人类的禽流感病毒，可以借助其他动物为“跳板”，逐渐进化成可以感染人类的病毒。早年间人们认为禽流感病毒只感染禽类，包括鸡、火鸡、鸭、鹅、鸽子、鹌鹑、鹦鹉等，从1997年发现人感染H5N1禽流感病毒至今，陆续出现H7N9、H5N6、H9N2、H10N8、H10N3等多种亚型禽流感病毒感染人事件。从历史资料和现有的研究资料表明，1918-2009年发生在人类的四次流感大流行，都涉及流感病毒基因重组后引起的跨种传播。2022年发现的猪流感病毒G4型，甚至存在禽、人和猪基因组“杂合”，具有大流行可能。这些现状提示构建流感病毒跨种传播预警系统的必要性，尤其活禽市场以及鸟类迁徙，这些都是防控禽流感传播的关键环节。没有人类吃煮熟的家禽（或蛋类）而感染禽流感的报道。

The influenza genome consists of 8 segments of RNA, which makes it mutate easily in the process of self-replication, often resulting in changes in the immunogenicity and antigenicity of the virus. This means that the bird flu virus, which cannot easily infect humans, can gradually evolve into a virus that can infect humans, especially with the help of other animals as a springboard. In the early years, it was believed that the avian influenza virus only infected birds, including chickens, turkeys, ducks, geese, pigeons, quails, and parrots. Since the H5N1 avian influenza virus was discovered in humans in 1997, a number of subtypes of avian influenza viruses, including H7N9, H5N6, H9N2, H10N8, and H10N3, have been reported to have infected humans. According to historical data and existing research data, the four influenza pandemics that occurred in humans from 1918 to 2009 all involved interspecies transmission caused by genetic recombination of influenza virus. The swine flu virus type G4, which was discovered in 2022, has a hybrid of poultry, human, and pig genomes, and has pandemic potential. These developments point to the need for an early warning system for inter-species transmission of influenza viruses, especially in live poultry markets and bird migration, which will be key elements in preventing the spread of avian influenza. There have been no reported cases of human infection from eating cooked poultry or eggs.

要理解流感病毒跨种传播，首先需要观察流感病毒的粒子结构。病毒表面有两类抗原蛋白：第一类是血凝素（Hemagglutinin，HA），有18种亚型；另一类是神经氨酸酶（Neuraminidase，NA），有11种亚型。流感病毒表面HA和NA是什么样的组合，就叫什么样的名字，这也就是为什么我们平时听到的流感名称都叫：HxNy。我们可以把HA想象成是流感病毒入侵宿主细胞时所需要的进门钥匙，而NA则是病毒破坏完毕，准备去入侵下一个动物细胞的出门钥匙。通常情况下，禽流感病毒的进门钥匙不能“解锁”人体呼吸道细胞的大门，但是流感病毒的特征就是变异很快，每一次基因重组就相当于是一次“改装”，忽然有一天，它可能就靠着“改装”后的钥匙打开了平常打不开的门，入侵了平常并不易感的动物。流感来势汹汹、“史无前例”。当然，流感病毒即使溜进细胞中，却也要经历多种挑战才能适应细胞微环境、并繁殖下一代，因此绝大多数会被宿主免疫系统消灭或自我衰亡，只有极少数流感病毒存活下来，这可能是基因突变使病毒复制能力或适应宿主的能力增强了，禽流感病毒因此具备了感染人的能力。

To understand the interspecies transmission of influenza viruses, we first need to look at the particle structure of influenza viruses. There are two types of antigenic proteins on the surface of avian influenza viruses: the first type is Hemagglutinin (HA), with 18 subtypes; the other is Neuraminidase (NA), which has 11 subtypes. The combination of HA and NA on the surface of the flu virus is called HxNy, which is why we often hear the flu name. Think of HA as the door key that the influenza virus needs to invade the host cell, and NA as the door key that the virus needs to destroy and move on to the next animal cell. Under normal circumstances, these keys can not “unlock” human respiratory cells, but one characteristic of influenza virus is to mutate quickly. If we think of each genetic recombination as equivalent to a modification, suddenly one day, the virus may one day modify the key to open a door that can not be opened normally, and invade normally unsusceptible animals. Of course, even when influenza viruses sneak into cells, they have to go through a variety of challenges to adapt to the cell microenvironment and reproduce. So most influenza viruses are destroyed by the host immune system or simply die. Very few influenza viruses survive, probably due to genetic mutations that increase the virus’s ability to replicate or adapt to the host. The bird flu virus thus has the ability to infect people.

从全球案例来看，禽类动物是流感病毒的巨大储存库，H7N9死亡率有40%，H5N1死亡率则高达60%，而且禽流感病毒时刻都有可能跨跃物种感染人类，也不乏可能，如2009年H1N1甲型流感突然从猪跨越到人类，导致人类流感大流行。好消息是，达菲是原本用来对抗禽流感的药物，事实证明对甲型流感的防控效果良好。疫苗接种是有效防控禽流感的第一道防线，但是随着病毒不断重组以及新毒株的不断呈现，导致疫苗的厂家需要不断更换毒株以匹配现有流行的病毒。值得高兴的是，反向遗传学等现代技术有力推进了禽流感病毒疫苗候选毒株的构建与快速研制。

Globally, birds are a huge reservoir of influenza viruses, which kill 40 percent of carriers of H7N9 and 60 percent of H5N1. Bird flu viruses can jump species to infect humans at any time, or, as in 2009, when the H1N1 avian flu suddenly jumped from pigs to humans, causing a human influenza pandemic. The good news is that Tamiflu, a drug originally used to fight bird flu, has proved effective against influenza A. Vaccination is an effective first line of defense against bird flu, but as the virus reorganizes and new strains emerge, vaccine manufacturers need to constantly change strains to match those currently circulating. Fortunately, modern techniques such as reverse genetics have facilitated the construction and rapid development of vaccine candidate strains of avian influenza virus.

PART 2: 传染性支气管炎病毒（Infectious bronchitis virus，IBV）

在电子显微镜下，冠状病毒粒子的表面有许多规则排列的突起，整个病毒就像一顶中世纪欧洲帝王的皇冠，因此被命名为“冠状病毒”。冠状病毒大家都不陌生，你知道第一个被发现的冠状病毒是1937年、从家禽体内分离出来的传染性支气管炎病毒IBV吗？IBV病毒可以感染多种禽类，如鸡、火鸡、麻雀、鸭、鹅、鸽子等。

Under the electron microscope, the surface of the coronavirus has many rod-shaped particle protrusions. The whole virus looks like a medieval European emperor’s crown, so it is named “coronavirus.” Coronavirus is no stranger. But did you know that the first coronavirus to be discovered was infectious bronchitis virus IBV, isolated from poultry in 1937? IBV virus can infect a variety of birds, such as chickens, turkeys, sparrows, ducks, geese, and pigeons.

IBV具有变异快、基因型多的特点，引起鸡的临床症状也较为复杂，像每个人都有自己的爱好一样，不同血清型IBV对感染不同组织各有偏好，一些毒株类型喜欢侵染呼吸系统，导致鸡有喘气、打喷嚏、和流鼻涕等典型呼吸道症状，我们称之为呼吸型；一些喜欢侵染肾脏，导致鸡腹泻，肾脏坏死、尿酸增多，我们称之为肾型；还有一些病毒倾向于攻击输卵管，导致鸡只产蛋量下降、产畸形蛋，我们称之为输卵管型。IBV一旦感染鸡群，甚至一夜之间大批量死亡，肾型IBV的死亡率远高于呼吸型。

IBV is characterized by rapid mutation, multiple genotypes, and complex clinical symptoms in chickens. Like everyone has his own hobbies, different serotypes of IBV have different preferences for infecting different tissues. Some strains like to infect the respiratory system, leading to typical respiratory symptoms such as panting, sneezing, and runny nose; these are called respiratory type. Some like to infect the kidney, resulting in chicken diarrhea, kidney necrosis, uric acid increase, and we call them kidney type; other viruses tend to attack the fallopian tubes, causing chickens to lower egg production and produce malformed eggs, and known as fallopian tube type. The mortality rate of renal IBV, which can kill overnight, is much higher than that of respiratory IBV.

IBV引起的传染性支气管炎在鸡群中具有高度传染性，对养殖业危害很大。IBV感染可能会对未成熟母鸡或后备母鸡造成永久伤害，影响后期产蛋量。IBV感染无特效药物治疗，疫苗接种是鸡传染性支气管炎防控方面最有效也是最重要的手段，但由于病毒基因型众多、流行时间长，其不同基因型毒株同时存在的情况下，新的变异株不断出现，为该病的防控带来了严峻挑战，对该病的防控将是一场持久战。

Infectious bronchitis caused by IBV is highly infectious in chickens and is very harmful to the breeding industry. IBV infection may cause permanent damage to immature or reserve hens, affecting later egg production. There is no specific drug treatment for IBV infection, so vaccination is the most effective and important means for the prevention and control of infectious bronchitis in chicken. However, due to the numerous viral genotypes and long epidemic time, mutant strains keep appearing when different genotypes of the virus exist simultaneously, which presents severe challenges for the prevention and control of the disease. The prevention and control of the disease will be a protracted war.

PART 3: 新城疫病毒（Newcastle disease virus，NDV）

你听说过新城疫吗？新城是英国地名，也是1927年首次分离到病毒的地方，的确，NDV病毒就是根据发源地而命名的，这也是早期研究中病毒命名的一种“惯例”。新城疫又称亚洲鸡瘟或伪鸡瘟，是一种高度接触性禽类烈性传染病，影响全球250多种禽类，包括鸽子、孔雀、野鸡、鸭和鹅等，其中以鸡最为易感。1946年，在美国和墨西哥首次发现NDV强毒株，野生候鸟和白鹳均很敏感。不仅是候鸟，一些圈养鸟类似乎也是NDV的天然宿主和易感宿主。NDV一般不感染人类，当然，接触禽类或生肉食品后最好立即彻底清洗双手。

Have you ever heard of Newcastle disease? Newcastle is a place name in the UK, where the virus was first isolated in 1927. Indeed, the NDV virus was named after its origin, which was a convention of virus naming in early research. Newcastle disease, also known as Asian Plague or pseudoplague, is a highly contagious infectious disease affecting more than 250 species of birds worldwide, including pigeons, peacocks, pheasants, ducks, and geese, among which chickens are the most susceptible. A virulent strain of NDV, to which wild migratory birds and storks are susceptible, was first identified in 1946 in the United States and Mexico. Not only migratory birds, but also some captive birds seem to be natural and susceptible hosts of NDV. NDV generally does not infect humans. Of course, it is best to wash your hands thoroughly immediately after handling poultry or raw meat.

科学家用电子显微镜可以看到新城疫病毒的样子。成熟的病毒粒子呈近圆形、或者蝌蚪形，基因组为单分子负链单股RNA，直径多数为180 nm左右。这个纳米要如何理解呢？打个比方，我们的一根头发，如果纵向能分成5万份的话，那每一份就是1纳米。那么小的一个病毒却会时不时引起鸡新城疫的发生，典型新城疫特征为发病急，呼吸困难，头冠紫黑，下痢，泄殖腔出血、坏死，以及十二指肠出血。由于疫苗的广泛应用，我国典型新城疫已较少见，但非典型新城疫却呈现上升趋势，主要表现为轻微呼吸道症状，发病率高但死亡率低，因此临床上很容易被忽视，从而耽误治疗的最佳时机，需要特别关注。

Scientists can use an electron microscope to see what Newcastle disease virus looks like. Mature virions are nearly round or tadpole shaped, and their genomes are single-molecule negative strand single-stranded RNA, most of which are about 180 nm in diameter. How do you understand a nanometer? For example, imagine a single strand of our hair, if divided into 50,000 lengthwise parts; the parts would be 1 nanometer each. Even a virus that small can cause Newcastle disease, which is characterized by rapid onset, difficulty breathing, chicken comb is in purplish black, dysentery, cloaca bleeding, necrosis, and duodenal bleeding. Due to the extensive application of vaccines, typical Newcastle disease has become rare in China, but atypical Newcastle disease is on the rise, mainly manifested as mild respiratory symptoms, with high morbidity but low mortality, so it is easy to ignore clinically, thus delaying past the best time for treatment, and requiring special attention.

此外，NDV还作为溶瘤病毒帮助人类治疗肿瘤。NDV选择性感染肿瘤细胞后，诱导的免疫反应和细胞内因子可以有效杀死肿瘤而不影响正常细胞。NDV最早在20世纪50年代就被报道具有溶瘤作用，目前多项临床研究证明了其作为溶瘤制剂和免疫治疗制剂的优势和巨大潜力。相信在未来，随着分子生物学和反向遗传技术的成熟，NDV抗肿瘤的治疗手段也将更加完善，也将拥有越来越广阔的应用前景。

Interestingly, NDVS help humans treat tumors, as oncolytic viruses. NDVS selectively infect tumor cells, inducing immune responses and intracellular factors that effectively kill tumors without affecting normal cells. NDV was first reported to have oncolytic effects in the 1950s, and a number of clinical studies have proved its advantages and great potential as an oncolytic agent and immunotherapy agent. It is believed that in the future, with the maturity of molecular biology and reverse genetic technology, the NDV anti-tumor treatment will be more perfect and have an increasingly broad prospect of application.

PART 4: 候鸟迁徙与病毒传播（Migratory bird migration and virus transmission）

禽流感通过候鸟的迁徙在世界范围内传播。岸鸟、海鸟和水鸟等很多物种会携带不同的禽流感毒株，当它们在迁徙途中聚在一起时，就会产生混合毒株，并随着候鸟的再次起飞将病毒传播出去。被感染鸟类的口腔或泄殖腔可能都会含有病毒，其他动物在吃了携带病毒的鸟类后也会被感染，浣熊、熊、狐狸、水貂，甚至海豹都被报道感染了禽流感。研究结果显示野生鸟类间发生过两波H5N1高致病性禽流感，已蔓延到其他物种，包括至少两次将病毒传给了海豹，之前主要通过鸟类传播的病毒正在威胁海洋哺乳动物。还有报道称，禽流感柬埔寨有一名11岁女孩死于禽流感。对于普通人来说，感染禽流感的风险是极低的，只有长时间与受感染的禽类近距离接触时，才会被感染，比如活禽摊主、饲养及运输活禽的工人等。人直接从野鸟处感染禽流感病毒是未见官方报道的，因此没必要见野鸟就杀，保持一定距离即可。

Bird flu spreads around the world through the migration of migratory birds. Many species, such as shorebirds, seabirds and water birds, carry different strains of bird flu, and when they assemble during migration, they create a mix of strains that can spread the virus as the birds take off again. Infected birds can have the virus in their mouths or cloaca, and other animals can become infected after eating infected birds. Raccoons, bears, foxes, minks, and even seals have all been reported infected. The results show that there have been two waves of the H5N1 highly pathogenic avian influenza among wild birds, which has spread to other species, including at least twice to seals, and that the virus, previously transmitted mainly by birds, is threatening marine mammals. There are also reports that an 11-year-old girl died of bird flu in Cambodia. For the general population, the risk of infection is extremely low; avian flu can only be acquired through prolonged close contact with infected birds. Owners of live poultry stalls and workers who raise and transport live poultry are more at risk. There have been no official reports of human infection from wild birds, so there is no need to kill wild birds, just keep a distance.

目前国际上一些国家研究，还通过候鸟进行NDV病毒感染传播的可能性，候鸟回迁，如带有野毒，可能引起基因型的变异，可导致病毒性传染病的流行。大量证据表明，IBV可以由家禽传播给野鸟，也可由野鸟传播给家禽，可利用候鸟主要迁徙所涉及区域的监测站资源，每年在野鸟流感监测的同时开展野生鸟类冠状病毒监测。

At present, some countries have studied the possibility of transmission of NDV virus through migratory birds. The migration of migratory birds, carrying wild virus, may cause genotype variation, which can lead to the prevalence of viral infectious diseases. There is substantial evidence that IBV can be transmitted from poultry to wild birds and from wild birds to poultry, and wild bird coronavirus surveillance should be conducted annually alongside wild bird influenza surveillance, using station resources in areas where migratory birds alight.

此外，预测流感暴发是未解难题，将地理信息学与分子生物学技术手段的全新结合，可通过从点连成线、再联接成网络，以候鸟携带病毒概率、候鸟存活概率、候鸟在目标区域出现/停留概率、候鸟与家禽有接触概率、候鸟与家禽有效接触概率、免疫覆盖率及免疫保护效率7个因素为主要风险节点，帮助人类摸清病毒的“航班网络”，构建我国家禽的风险评估模型。野生鸟类将病毒传播至世界各地，其迁徙模式决定了病毒下一次传播的时间和地点。相关部门需要密切监测候鸟，并提高养殖场的防护水平，尽量避免家禽与野禽接触。

Predicting influenza outbreaks is an unsolved problem, and a novel combination of geoinformatics and molecular biological techniques can be used. By connecting dots and reconnecting them into networks, , we have begun to understand the “flight network” of the virus and build a risk assessment model for domestic poultry. The seven main risk nodes were found to be the probability of migratory birds carrying the virus, the probability of survival of migratory birds, the probability of presence/stay of migratory birds in the target area, the probability of contact between migratory birds and poultry, the probability of effective contact between migratory birds and poultry, the immunization coverage rate, and the efficiency of immune protection. Wild birds spread the virus around the world, and their migration patterns determine when and where the virus will spread next. Authorities need to closely monitor migratory birds and improve the level of protection on farms to avoid contact between poultry and wild birds.

总编辑：牛立辰

文本：游婧玲，王晓佳

翻译：王晓佳

导演及编辑：刘佳茵

解说：雷逸雪