Stokes C R, Finerty S, Gruffydd-Jones T J, Sturgess C P, Harbour D A
Division of Molecular and Cellular Biology, University of Bristol, UK.
J Biotechnol. 1999 Aug 20;73(2-3):213-21. doi: 10.1016/s0168-1656(99)00139-x.
Feline immunodeficiency virus (FIV) infection is a naturally occurring lentiviral infection of cats which progresses to immunodeficiency in a manner strikingly similar to that observed in HIV infection in man. The rectal and cervico-vaginal mucosae are common routes of transmission of HIV and it has been shown that the gastrointestinal tract is an important site of HIV infection and primary pathology. Although biting is the principle mode of transmission for FIV, we have shown that it is possible to reliably infect cats via both the rectal and vaginal routes. Using a biotin-streptavidin linked immunoperoxidase technique we have detected FIV core and envelope proteins in the colonic follicle associated epithelial cells, cells within the lymphoid follice and occasional cells in the lamina propria. Further, in the intestine we have detected FIV RNA and proviral DNA in epithelial cells, colonic lymphoid aggregates and isolated lamina propria cells. We have studied a group of asymptotic cats which have been rectally infected with FIV for 1 year or longer and shown an increase in the number of lamina propria CD8+ cells and greater levels of IL-2, IL-6, IL-10 and gamma-IFN mRNA. Since these cats remained clinically healthy these results might suggest that both local antibody and class I restricted cytotoxic lymphocytes (CTLs) may play a role in control of viral replication. We have investigated a range of vaccination regimes for their ability to generate responses which would protect from rectal challenge with virulent virus. Cats have been immunized with whole virus (FIV-pet, FIV-GLA-8), V3, V3MAP or C2 with cholera toxin (CT), or Quil A based adjuvants via rectal, intra-nasal, parenteral or targeted lymph node routes, and challenged rectally with ten mucosal cat infectious doses (MCID) of FIV-GLA-8. We have shown that the adjuvant effects of cholera toxin and Quil A are not influenced by the route of delivery (intraperitoneal (i.p.) versus rectal) with CT more effective in stimulating humoral and Quil A more effective in stimulating cellular responses to FIV antigens. However we have shown that, quantitatively, CT is more effective when used as an adjuvant via the intra-nasal than the rectal route. Recently, we have begun to investigate if the promising results obtained with targeted lymph node (TLN) vaccination in monkeys could be reproduced in the cat. We have shown that TLN was more effective than rectal immunisation in stimulating both humoral and proliferative responses. In a preliminary study we have also been able to detect FIV specific CTLs and have observed protection from rectal challenge in four out of four cats.
猫免疫缺陷病毒（FIV）感染是猫自然发生的慢病毒感染，其发展为免疫缺陷的方式与人类HIV感染极为相似。直肠和宫颈 - 阴道黏膜是HIV常见的传播途径，并且已经表明胃肠道是HIV感染和原发性病理的重要部位。虽然咬伤是FIV的主要传播方式，但我们已经证明通过直肠和阴道途径可靠地感染猫是可能的。使用生物素 - 链霉亲和素连接的免疫过氧化物酶技术，我们在结肠滤泡相关上皮细胞、淋巴滤泡内的细胞以及固有层中的偶见细胞中检测到了FIV核心蛋白和包膜蛋白。此外，在肠道中，我们在上皮细胞、结肠淋巴聚集物和分离的固有层细胞中检测到了FIV RNA和前病毒DNA。我们研究了一组经直肠感染FIV达1年或更长时间的无症状猫，发现固有层CD8 +细胞数量增加，IL - 2、IL - 6、IL - 10和γ - IFN mRNA水平升高。由于这些猫临床上保持健康，这些结果可能表明局部抗体和I类限制性细胞毒性淋巴细胞（CTL）可能在控制病毒复制中起作用。我们研究了一系列疫苗接种方案，以评估它们产生能够抵御强毒病毒直肠攻击的免疫反应的能力。猫通过直肠、鼻内、肠胃外或靶向淋巴结途径用全病毒（FIV - pet、FIV - GLA - 8）、V3、V3MAP或C2与霍乱毒素（CT）或基于Quil A的佐剂进行免疫，并以10个黏膜猫感染剂量（MCID）的FIV - GLA - 8进行直肠攻击。我们已经表明霍乱毒素和Quil A的佐剂效果不受给药途径（腹腔内（i.p.）与直肠）的影响，CT在刺激体液反应方面更有效，而Quil A在刺激对FIV抗原的细胞反应方面更有效。然而，我们已经表明，从数量上看，CT通过鼻内途径用作佐剂比通过直肠途径更有效。最近，我们开始研究在猴子中通过靶向淋巴结（TLN）疫苗接种获得的有前景的结果是否能在猫中重现。我们已经表明TLN在刺激体液和增殖反应方面比直肠免疫更有效。在一项初步研究中，我们还能够检测到FIV特异性CTL，并观察到四只猫中有四只在直肠攻击中受到保护。
