Investigations of filovirus propagation and cellular defense mechanisms against filoviruses in the reservoir host Rousettus aegyptiacus and other fruit bat species

马尔堡病毒（MARV）和埃博拉病毒（EBOV）都是丝状病毒科的成员，存在于中非的果蝠体内，并在人群中引起零星爆发。人类的丝状病毒感染会导致严重的出血热，病死率很高，相比之下，果蝠，丝状病毒的天然宿主似乎没有表现出症状。人丝状病毒的主要靶细胞是单核细胞、巨噬细胞和树突细胞。它们在先天性和适应性免疫中的功能受损导致大量细胞因子分泌和由丝状病毒引起的疾病的严重性。目前还不清楚果蝠来源的单核细胞、巨噬细胞和树突状细胞是否对丝状病毒感染敏感，以及它们是否在感染过程中起决定性作用。不同的果蝠物种被描述为EBOV和MARV的潜在宿主。在三种不同的果蝠物种中检测到EBOV特异性抗体：锤头果蝠、Franquet's Epauletted果蝠和小领果蝠。在另一种果蝠物种埃及果蝠中发现了MARV特异性RNA和抗体，到目前为止，这是唯一分离出传染性MARV的物种。MARV和EBOV在埃及果蝠的细胞中增殖得不一样。因此，我们推测，病毒特异性的差异决定了它们在特定的果蝠细胞中复制的能力。I型干扰素（IFN）系统是第一个有效的细胞防御机制，对病毒和大多数病毒开发的计数器策略，抑制IFN系统，使病毒复制。病毒蛋白抑制IFN应答的能力的种属特异性差异可能与病毒对新宿主的适应有关。目前还不清楚丝状病毒IFN拮抗剂（VP35、VP40和VP24）控制果蝠的IFN系统，以及种特异性差异是否可能导致病毒在储存宿主中的致病性比受体宿主低。然而，这些差异对于理解丝状病毒在人类中的致病性和蝙蝠的免疫系统是很重要的，蝙蝠的免疫系统能够传播许多引起人类严重疾病的病毒。我们想研究（i）果蝠的永生细胞和原代细胞对丝状病毒感染的反应，（ii）不同病毒株在果蝠细胞中的繁殖，（iii）果蝠衍生细胞中对丝状病毒的细胞防御机制。

Marburg virus (MARV) and Ebola viruses (EBOV), both members of the family Filoviridae, reside in fruit bats in Central Africa and cause sporadic outbreaks in the human population. Filoviral infections in humans lead to a severe hemorrhagic fever with high case-fatality rates, in contrast, fruit bats, the natural reservoir for filoviruses do not seem to show symptoms. Primary target cells for filoviruses in humans are monocytes, macrophages and dendritic cells. Impairment of their function in innate and adaptive immunity leads to massive cytokine secretion and severity of the disease caused by filoviruses. Currently it is not known whether fruit bat derived monocytes, macrophages and dendritic cells are susceptible to filovirus infection and if they play a decisive role during the course of infection.Distinct fruit bat species are described as the potential reservoir for EBOV and MARV. EBOVspecific antibodies were detected in three different fruit bat species: the Hammer-headed Bat, Franquet’s Epauletted Fruit Bat and Little Collared Fruit Bat. MARV-specific RNA and antibodies were found in another fruit bat species the Egyptian Fruit Bat and so far, this is the only species from which infectious MARV has been isolated. MARV and EBOV proliferate unequally well in cells from the Egyptian Fruit Bat. Therefore we presume that virus-specific differences determine their capability to replicate in a specific fruit bat cell.The type-I-interferon (IFN) system is the first effective cellular defense mechanism against viruses and most viruses developed counter strategies that inhibit the IFN system to allow viral replication. Species-specific differences in the capability of viral proteins to inhibit the IFN response can be relevant for the adaptation of viruses to a new host. Nothing is known so far on how the filoviral IFN antagonists (VP35, VP40 and VP24) control the IFN system of fruit bats and whether speciesspecific differences might contribute to reduced pathogenicity of the virus in the reservoir host in comparison to the recipient host.Taken together, very little is known about the differences between reservoir host and recipient species in terms of their ability to replicate or restrict filoviruses. These differences, however, are important to understand on the one hand the pathogenicity of filoviruses in humans and on the other hand the immune system of bats that are able to propagate many viruses that induce severe diseases in men. We would like to investigate (i) the response of immortalized and primary cells of fruit bats to filovirus infection, (ii) the propagation of different virus strains in fruit bat cells, (iii) cellular defense mechanisms against filoviruses in fruit bat derived cells.