犬副流感病毒（CANINE PARAINLUENZAVIRUS）
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CANINE PARAINLUENZAVIRUS Canine parainfluenzavirus (CPIV) was first reported in the late l 960s from laboratory dogs with respiratory disease and from a sentry dog with respiratory disease of the upper tract． Subsequent studies revealed that the virus was frequent in dogs with respiratory disease， suggesting a key role，along with Bordetella bronchiseptica，in the aetiology of ITB． Parainfluenza viruses include important pathogens of respiratory tract of mammals and birds．The term parainfluenza was originaNy adopted after the influenza——like symptoms observed in infected patients and after the influenza——like hemagglutination and neuraminidase activities exhibited by the virus particles．Parainfluenza viruses are classified in the family Paramyxoviridae， subfamily Paramyxovirinae． CPIV is antigenically similar to the simian virus 5 (SV5)and to porcine，bovine，ovine and feline parainfluenza viruses．Sequence analysis of the fusion protein——encoding gene has revealed that CPIV has 99．3％nucleotide similarity to procine parainfluenza virus．98．5％to SV5 and 59．5％nt to human parainfluenza virus 2．Accordingly，CPIV is regarded as a host variant of SV5，within the genus Rubulavirus and has been tentatively proposed as parainfluenza virus 5(P1一5)．Viruses genetically similar to SV5 have been detected in humans in more occasions although the relationship to any human disease remain contentious． The virus is composed of a single stranded RNA genome of negative polarity and is surrounded by a lipid envelope of host cell origin．The genome of SV5 contains seven genes that encode eight proteins： the nucleoprotein (NP)， V／ phosphoprotien(v／P)，matrix(M)，fusion(F)， small hydrophobic (SH)，hemagglutinin— neuraminidase(HN)，and large(L)genes．The HN protein is involved in cell attachment to initiate virus irifection and mediates hemagglutination． In addition，HN has neuraminidase activity．The F protein mediates fusion of the viral envelope with the cell membrane．The V protein blocks interferon(IFN) signaling and inhibits IFN synthesis．Interaction of the virus with the IFN system is regarded as a critical factor in the outcome of the infection． Parainfluenza is highly contagious and the prevalence of infection appears to be related to the density of the dog population．CPIV is excreted from the respiratory tract of infected animals for 8—1 0 days after infection and is usually transmitted by direct contact with infected aeros01．The virus may spread rapidly in kennels or shelters where a large number of dogs are kept together．The virus was detected in l 9．4％of tracheal and 9．6％of lung samples of dogs in rehoming centre where ITB was endemic and persisted，in spite of regular vaccination against canine adenovirus type一2， distemper and parainfluenza． There is evidence that cats，hamsters and guinea pigs may naturally be infected with CPIV／SV5 0r a very closely related virus．In addition，a CPIV／ SV5一like strain，terms SER，was recently isolated from the lung of a fetus of a breeding sow with porcine respiratory and reproductive syndrome． Antibodies to CPIV have been demonstrated in 20 0f 44 wildlife species in eight African countries．Als0，antibodies to CPVI have been detected in non——captive black bears and fishers in Canada，suggesting circulation of CPIV—like L中国宠物医师网'n*N?+ZgOg P/{
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viruses in wildhfe animals． Even more interestingly，CPIV／SV5一like viruses may infect humans and non—human primates． CPIV infection is usually restricted to the upper respiratory tract in dogs of two weeks of age or older． Although viremia is considered an uncommon event，CPIV has been recovered from the lungs，spleen，kidneys and liver of laboratory dogs with mixed infection．After experimental infection of dogs，CPIV replicates in cells of the nasal mucosa，pharynx，trachea and bronchi．Small amounts of virus can be recovered from the local lymph nodes，but not from other lymphatic tissues．In naturally infected dogs，simultaneous infections with other viral and bacterial agents are quite common and clinical signs may be more Severe． Symptoms generally occur 2——8 days after infection．CPIV produces mild symptoms lasting less than six days，but infection is usually complicated by other pathogens．In the non— complicated forms，clinical signs include low— grade rise in temperature，deep sounding dry cough，watery nasal discharge，pharyngitis and tonsillitis．Most dogs appear healthy and active．In the complicated forms，described mostly in immunocompromised animals or young unvaccinated puppies，the symptoms may progess and include lethargy，fever，inappetence，and pneumonia． CPIV has also been isolated from a dog with temporary posterior paralysis and this isolate， termed CPI+，caused acute encephalitis when injected intracranially into gnotobiotic dogs．From one such experimentally infected d09，a variant， termed CPl2，was isolated that had phenotypic and genotypic differences from CPI+．CPl2 is attenuated in ferrets and it more readily establishes persistent infections in tissue culture cells．The biological change and the ability to block I FN signaling have been mapped to the P／V——N—— terminal common domain of the V protein． In experimentally infected dogs petechial hemorrhages have been described in lung lobes between 3 and 8 days post infection．Histological examination has revealed catarrhal rhinitis and tracheitis with mon0——and polymorphonuclear cell infiltrates in the mucosa and submucosa． Bronchi and bronchioli may contain leukocytes and cellular debris． Laboratory diagnosis may rely on viral isolation from nasopharyngeal or laryngeal swabs，using primary cells or cell lines derived from dog kidneys．A wide range of canine，feline，bovine， simian，and human cells are permissive for CIPV and monkey kidney cells have also been used successfully．In the first passage，the virus usually does not induce cytopathic effects and virus antigens may be demonstrated by hemadsorption or immunofluorescence．RT—PCR may also be applied to respiratory secretions，nasopharyngeal／ laryngeal swabs and tracheal／lung tissues． Serological investigations by hemagglutination inhibition and the virus neutralization test may be useful to screen animals for the presence of specific antibodies． Attenuated vaccines have been developed against CPIV．A parenteral CPIV vaccine is available in combination with other antigens．These vaccines alone rarely provide protection against contracting the infection，although they help to reduce the severity of the disease．Vaccination of all animal， notably of puppies，is indicated in kennels or in pet shops．Strict hygiene with thorough cleaning and disinfection of cages and food and water containers， good ventilation and adequate population density are essential for controlling virus spread．8[
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犬副流感病毒(CPIV)最早于20世纪60年 代在1只出现呼吸疾病的试验犬和l只上呼吸 道有呼吸疾病的放哨犬中有过报道。后来研究 发现，在犬的呼吸疾病中，该病毒很普遍，提示 其在ITB病原学中与支气管败血博氏杆菌有同 样的作用。中国宠物医师网"~oE5i]n!A
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副流感病毒是哺乳动物和鸟类呼吸道的重 要病原。“副流感病毒”原来指感染者出现流感 病毒感染的类似症状以及病毒颗粒呈现流感病 毒类似的血凝作用和神经氨酸苷酶活性。副流 感病毒属于副粘病毒科副粘病毒亚科成员。中国宠物医师网7e@tR!t4wH.}
e O C0K'B0CPIV抗原性类似猿病毒5型(SV5)以及猪、牛、 羊和猫副流感病毒。融合蛋白编码的基因进行 序列分析后发现，CPIV与猪副流感病毒的核苷 酸有99．3％的同源性，与SV5有98．5％的同源 性，与人副流感病毒2型有59．5％的同源性。因 此，CPIV被认为是腮腺炎病毒属的SV5的变异 型，曾尝试提议为副流感病毒5型(PI-5)。该病 毒与人类中发现的SV5基因型多相似，但是该 病毒与人类疾病的关系仍然存在争议。([cmD2^+c r0
!Kf!C G\&pwuas0病毒由单股、负链RNA构成，并且外周存 在宿主细胞起源的脂质包裹体。SV5基因组包 含7个基因片段，编码8个蛋白，分别是：核蛋 白(NP)、V／磷蛋白(V／P)、基质蛋白(M)、融合 蛋白(F)、小疏水蛋白(SH)、血凝素一神经氨酸 苷酶蛋白(HN)和大基因蛋白(L)。HN蛋白参 与原始病毒粘附到细胞表面的过程并介导血凝 作用。此外，HN还具有神经氨酸苷酶活性。F蛋 白发挥融合病毒包括体和感染细胞膜的作用。v 蛋白阻止干扰素(IFN)的信号传导，并阻止IFN 的合成。病毒与IFN系统的相互作用是感染发 生的重要因素。中国宠物医师网"c5e-f*e/yG6t
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副流感病毒具有高度传染性，感染的流行程 度似乎和全群的密度有关。CPIV由动物感染病 毒的8～10天后的呼吸道中分泌出来，通常通过 感染的气溶胶进行直接传播。病毒在犬窝或大 量犬集中的场所中可能迅速传播开来。在ITB 流行和持续发病的收养中心里，l9．4％的犬从气 管中能分离到该病毒，9．6％的犬从肺脏样品中 能分离到该病毒，尽管这些犬都进行过犬腺病 毒2型、犬瘟热和副流感病毒的常规免疫。中国宠物医师网
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_B]%]ap U'D0有事实证明，猫、仓鼠和天竺鼠能自然感染 CPIV／SV5或者非常相近的病毒。此外，CPIV／ SV5相近的毒株，命名为SElL，近来在患猪繁殖 与呼吸障碍综合征的哺乳母猪的幼仔中分离得 到。在8个非洲国家的44个野生动物种类中有 20个都证实存在CPIV抗体。同时，在加拿大的 非捕获的黑熊和食鱼动物中也发现了CPIV抗 体，提示CPIV相近的病毒在野生动物中存在流 行。更有趣的是，CPIV／SV5相近病毒可能会感 染人类或非人类的灵长类。_+XYQuc$l0
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2周龄及其以上年龄的犬感染CPIV病毒 后，往往局限在上呼吸道。尽管病毒血症一般不 常见，但是曾在混合感染的试验犬的肺脏、脾 脏、肾脏和肝脏中发现CPIV。病毒通过试验感 染犬后，CPIV在鼻腔粘膜、咽、气管和支气管细 胞中进行复制。在局部淋巴结中可以发现少量 的病毒，但是在其他淋巴组织中并不能发现病 毒。在自然感染的患犬中，同时感染其他病毒或 细菌比较常见，且临床症状可能会更加严重。.@*Dd RB Ls1Q8f0
K^)^8or&r1p0病毒感染后一般2～8天出现临床症状。X9ag-z.j&X I)fjt#B0
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CPIV产生温和的临床症状，且持续时问少于6 天，但是当和其他病原同时感染时，就会出现复 杂的临床症状。在温和型中，临床表现包括体温的略微上升，声音低沉的干咳、水样鼻腔分泌 物、咽炎和扁桃体炎。大多数犬表现健康、活泼。中国宠物医师网j+F-tQ4B
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复杂型通常大多数发生在免疫力低弱的犬或年 轻、未进行过免疫的幼犬中，症状渐进性加重， 出现精神倦怠、发热、食欲不振和肺炎症状。中国宠物医师网Sr*N6]7i+Z4BV U4S|h
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在暂时性尾部麻痹的患犬体内分离到的 CPIV，命名为CPI+，通过脑内注射到限菌的犬 中，可以导致急性脑炎。从这只试验患犬体内分 离到l株变异的，与CPI+相比具有不同表型和 遗传型的病毒，命名为CPl2。CPl2可以在雪貂 体内致弱，并且在组织培养细胞中很容易持续 感染。病毒的生物学特性变化及其阻止IFN信 号通路的能力在V蛋白区域P／v的N末端有 所体现。中国宠物医师网*K KcGma*S#l
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在感染的3～8天后，试验患犬的肺叶中发现 有出血瘢。组织学检查发现存在卡他性鼻炎和 气管炎，粘膜和粘膜下有单核白细胞及多核白 细胞浸润。支气管和细支气管可能存在白细胞 和细胞碎片。-B{TOf!l5ud0
)NY*N#FL/J `Sx0实验室诊断可以根据鼻咽拭子或喉拭子的 病毒分离来进行，应用犬肾原代细胞或细胞系 进行病毒培养。犬、猫、牛、猿和人的多种细胞易 感CIPV，且猴。肾细胞也曾成功应用。开始时，病 毒一般都不导致细胞病变反应，病毒抗原可能 通过红细胞吸附或免疫荧光试验来进行证实。 o1Pij&Os
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对呼吸分泌物、鼻咽拭子／喉拭子以及气管／肺 脏组织应用RT-PCR也可证实病毒的存在。通 过血凝抑制试验和病毒中和试验的血清学调查 在筛查存在特异性抗体的动物的过程中可发挥 一定作用。中国宠物医师网 iti#M Dg,^
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目前已经有了CPIV的致弱疫苗，肠道外的 CPIV疫苗与其他一些抗原疫苗都已经上市。这 些疫苗单独使用时，很少能控制感染发生，但是 能减轻疾病的严重程度。应该对犬窝和宠物店 的所有动物，尤其是幼仔，进行免疫接种。对犬 舍、食物容器和水容器进行彻底清洁和消毒的 严格卫生措施，良好的通风、适当的饲养密度都 是控制病毒传播的基础。中国宠物医师网&^8n d"s&Sn
