《2017 [Current Topics in Microbiology and Immunology]__ Host Factors in Coronavirus Replication》由会员分享，可在线阅读，更多相关《2017 [Current Topics in Microbiology and Immunology]__ Host Factors in Coronavirus Replication（42页珍藏版）》请在金锄头文库上搜索。
1、Host Factors in Coronavirus Replication Adriaan H. de Wilde, Eric J. Snijder, Marjolein Kikkert and Martijn J. van Hemert Abstract Coronaviruses are pathogens with a serious impact on human and animal health. They mostly cause enteric or respiratory disease, which can be severe and life threatening,
2、 e.g., in the case of the zoonotic coronaviruses causing severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in humans. Despite the economic and societal impact of such coronavirus infections, and the likelihood of future outbreaks of additional pathogenic coronaviru
3、ses, our options to prevent or treat coronavirus infections remain very limited. This high- lights the importance of advancing our knowledge on the replication of these viruses and their interactions with the host. Compared to other +RNA viruses, coronaviruses have an exceptionally large genome and
4、employ a complex genome expression strategy. Next to a role in basic virus replication or virus assembly, many of the coronavirus proteins expressed in the infected cell contribute to the coronavirus-host interplay. For example, by interacting with the host cell to create an optimal environment for
5、coronavirus replication, by altering host gene expres- sion or by counteracting the hosts antiviral defenses. These coronavirushost interactions are key to viral pathogenesis and will ultimately determine the outcome of infection. Due to the complexity of the coronavirus proteome and replication cyc
6、le, our knowledge of host factors involved in coronavirus replication is still in an early stage compared to what is known for some other +RNA viruses. This review summarizes our current understanding of coronavirushost interactions at the level of the infected cell, with special attention for the a
7、ssembly and function of the viral RNA-synthesising machinery and the evasion of cellular innate immune responses. A.H. de Wilde ? E.J. Snijder ? M. Kikkert ? M.J. van Hemert ( Ksiazek et al. 2003; Kuiken et al. 2003; Peiris et al. 2003), which resulted in 8000 laboratory-confi rmed cases and 774 ass
8、ociated deaths worldwide (WHO 2004). Although in terms of death toll not comparable to infl uenza, HIV or HCV, the 2003 SARS-CoV outbreak caused worldwide public concern and seriously affected the global economy estimated losses $30100 billion; (Keogh-Brown and Smith 2008). SARS-CoV initially causes
9、 lower respiratory tract disease, which can lead to a progressive and potentially lethal atypical pneumonia with clinical symptoms that include fever, malaise, lymphopenia, and in some cases also diarrhea. Two years after the outbreak, horseshoe bats were identifi ed as the likely reservoir of the S
10、ARS virus, whereas civet cats probably have served as intermediate host during the zoonotic transfer to humans (Lau et al. 2005; Li et al. 2005b). Adaptation to the human host required a small number of mutations in the receptor-binding domain of the SARS-CoV spike (S) protein, which mediates cell b
11、inding and entry (Li et al. 2005c) (see Chap. 2). There is increasing evidence that SARS-like coronaviruses continue to circulate in bats and that these may have the potential to readily cross the species barrier and emerge as human pathogens (Ge et al. 2013; Menachery et al. 2015). Such zoonotic sc
12、enarios therefore remain a serious public health concern. Almost a decade after the SARS-CoV outbreak, the next zoonotic coronavirus emerged: Middle East Respiratory Syndrome coronavirus (MERS-CoV) (de Groot et al. 2013). The virus was fi rst isolated in June 2012 from a 60-year-old Saudi Arabian ma
13、le who died from acute respiratory distress syndrome (ARDS) and multiple organ failure, including renal failure (Zaki et al. 2012; van Boheemen et al. A.H. de Wilde et al. 2012). Also MERS-CoV can cause a lower respiratory tract infection with symp- toms that include coughing and high fever. By the
14、end of 2016, more than 1850 laboratory-confi rmed MERS-CoV cases had been recorded, with a mortality rate of about 35% (WHO 2016). MERS-CoV is assumed to be transmitted to humans from camels and serological studies in the latter animals revealed that they have harbored MERS-CoV or MERS-CoV-like viru
15、ses for decades (Muller et al. 2014). Besides the zoonotic SARS- and MERS-CoVs, the coronavirus family includes four established human coronaviruses (HCoVs), of which HCoV-OC43 and -229E have already been known since the 1960s. These two viruses cause mild respiratory disease and, after rhinoviruses
16、, are a leading cause of common colds (1030% of the cases) (van der Hoek 2007; McIntosh et al. 1967; Hamre and Procknow 1966). More recently, following intensifi ed screening for coronaviruses, two additional HCoVs were discovered, HCoV-NL63 (van der Hoek et al. 2004) and HCoV-HKU1 (Woo et al. 2005). Interestingly, recent fi ndings suggest that also HCoV-NL63, -229E, and -OC43 originate from zoonotic transfer from bats (Huynh et al. 2012; Corman et al. 2016; Vijgen et al. 2006; Corman et al. 20
