Coronavirus spike proteins in viral entry and pathogenesis.
Coronavirus spike proteins in viral entry and pathogenesis.
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DOI：
10.1006/viro.2000.0757
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发表时间：
2001-01-20
期刊：
影响因子：
3.7
通讯作者：
Buchmeier MJ
中科院分区：
文献类型：
--
作者：
Gallagher TM;Buchmeier MJ
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Coronaviruses comprise a large and diverse family of enveloped, positive-stranded RNA viruses. The Coronaviridae exhibit broad host range, infecting many mammalian and avian species and causing upper respiratory, gastrointestinal, hepatic, and central nervous system diseases. In humans and fowl, coronaviruses primarily cause upper respiratory tract infections, while porcine and bovine coronaviruses establish enteric infections that result in severe economic loss. Coronaviruses of laboratory mice are, for historical reasons, designated as mouse hepatitis viruses (MHVs), but among these only a subset are strictly hepatotropic. Enteric strains are commonly found in rodent colonies and neurotropic strains are exploited to study central nervous system infection and demyelinating disease (Perlman et al., 2000). The extraordinary variations in host range and tissue tropism among coronaviruses are in large part attributable to variations in the spike glycoprotein. The S protein is a large, type I membrane glycoprotein that contains distinct functional domains near the amino (S1) and carboxy (S2) termini. These spikes function to define viral tropism by their receptor specificity and perhaps also by their membrane fusion activity during virus entry into cells. Recently their natural variation has attracted the attention of researchers interested in determinants of viral host range, virus entry, and virus–receptor interactions and their relationship to tropism. Evidence supporting a role for spike protein projections as agents of organ tropism and pathogenesis began with comparative studies of different naturally occurring MHV strains. In essence, nucleotide sequencing revealed that alterations in virus virulence were most closely associated with differences in the spike gene. These correlative findings were recently reinforced using the new technology of targeted RNA recombination, a strategy that can introduce site-specific mutations into the 27-to 32-kb RNA genome via recombination with defined in vitro transcripts. With a collection of carefully constructed recombinant coronaviruses differing only in the spike gene, the relationship between spike variation and in vivo pathogenesis has been unequivocally established (Sanchez et al., 1999; Phillips et al., 1999; Kuo et al., 2000).The challenge now is to understand, in mechanistic terms, how mutations in spike proteins alter in vivo virulence. This challenge is difficult in the absence of structural data for any S protein. What is known is that the peripheral S1 portion can independently bind cellular receptors while the integral membrane S2 portion is required to mediate fusion of viral and cellular membranes (Fig. 1). While natural genetic variability is most extreme in the S1 fragment, S2 changes are also found in mutants with novel in vivo infection characteristics. Thus, it is likely that both the receptor recognition and membrane fusion properties must be investigated for a complete view of coronavirus pathogenesis. The distribution of coronavirus receptors is critical to the pathogenic outcome. In this regard, it is notable that coronavirus spikes exhibit a range of receptor specificities; MHVs enter after binding members of a pleiotropic family of carcinoembryonic antigen–cell adhesion molecules (CEACAMs); feline and porcine coronaviruses bind metalloproteases; and bovine coronaviruses recognize 9-O-acetylated sialic acids (Holmes and Dveksler, 1994). Without detailed structural data for spikes or these receptors, insights into this initial entry stage have relied largely on identifying the minimal spike and receptor peptide fragments required for binding. These studies are relatively advanced for the MHVs, where it is known that an …
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影响因子：
5.4
作者：
Gallagher, TM
通讯作者：
Gallagher, TM
影响因子：
5.4
作者：
GALLAGHER, TM;ESCARMIS, C;BUCHMEIER, MJ
通讯作者：
BUCHMEIER, MJ
影响因子：
5.4
作者：
Saeki, K;Ohtsuka, N;Taguchi, F
通讯作者：
Taguchi, F
影响因子：
5.4
作者：
Baric, RS;Yount, B;Chen, W
通讯作者：
Chen, W
DOI：
10.1073/pnas.90.5.1716
发表时间：
1993-03-01
影响因子：
11.1
作者：
DVEKSLER, GS;PENSIERO, MN;HOLMES, KV
通讯作者：
HOLMES, KV