A study on the prevention and treanment of feline immunodeficiency virus infection

对从日本多个地区获得的猫免疫缺陷病毒(FIV)env基因的核苷酸序列分析表明，日本东部和西部地区分别以B和D亚型病毒为主，个别地区偶尔发现A和C亚型病毒。分离并鉴定了猫CC-和CXC-趋化因子的分子克隆，它们是HIV辅助受体的配基。在这些趋化因子中，SDF-1β可抑制猫T淋巴样细胞中FIV的生长。此外，新合成的与CXC-趋化因子受体结合的化合物T22也抑制了FIV的生长，另一方面，FIV感染诱导的细胞凋亡在免疫缺陷的发病机制中发挥了重要作用。体外实验表明，抗氧化剂N-乙酰半胱氨酸和抗坏血酸可抑制流感病毒感染诱导的细胞凋亡。此外，将IL-12和IL-10加入苍蝇体外诱导细胞凋亡系统中。IL-12可抑制FIV增殖和细胞凋亡，而IL-LO则无此作用。IL-12对病毒增殖和细胞凋亡的抑制作用是通过干扰素-γ的表达来实现的。接下来，为了检测这些化合物对FIV生长和细胞凋亡的抑制作用，用QC-PCR法测定了感染苍蝇的猫的血浆病毒RNA载量，结果表明，无症状携带期的猫血浆病毒RNA载量小于105拷贝/毫升，而艾滋病猫的血浆病毒RNA载量高于107拷贝/毫升。利用血浆FIV RNA定量系统，我们正在继续研究FIV感染猫体内病毒RNA载量的动态变化和抗病毒药物的作用。

Nucleotide sequence analysis of feline imunodeficiency virus (FIV) env gene obtained from multiple districts in Japan showed that subtypes B and D viruses were predominant in the eastern and western parts of Japan, respectively, and subtypes A and C viruses were occasionally found in some specific areas. Molecular clones of feline CC-and CXC-chemokines, which have been identified as ligands of co-receptors for HIV, were isolated and characterized. Of these chemokines, SDF-1beta was shown to inhibit the growth of FIV in cat T-lymphoid cells. Moreover, T22, a newly synthesized compound which binds to CXC-chemokine receptor, also inhibited FIV growth.On the other hand, apoptosis induced by FIV infection is known to play an important role for the pathogenesis of immunodeficiency. Antioxidants, N-acetylcysteine and ascorbic acid, were shown to inhibit apoptosis induced by FlV infection in vitro. Furthermore, IL-12 and IL-10 were added to the in vitro apoptosis-induction system by Fly. IL-12 was shown to inhibit FIV growth and apoptosis, however, IL-lO did not have such effect. The inhibitory effect of IL-12 for virus growth and apoptosis was found to be mediated by the expression of IFN-gamma.Next, to examine the effect of these compounds for inhibition of FIV growth and apoptosis, plasma viral RNA load in FLY-infected cats was quantified with QC-PCR.As a result, the plasma viral RNA load was less than 105 copies/ml in cats in asymptomatic carrier stage but higher than 107 copies/ml in cats in AIDS stage. By using the quantification system for plasma FIV RNA, we are continueing the investigation on the kinetics of the viral RNA load and effect of anti-viral drugs in FIV-infected cats.