Highly infectious SARS-CoV pseudotyped virus reveals the cell tropism and its correlation with receptor expression

Nie, Yongzhan; Wang, Peigang; Shi, Xuanling; Wang, Guangwen; Chen, Jian; Zheng, Aihua; Wang, Wei; Wang, Zai; Qu, Xiuxia; Luo, Min; Tan, Lianjiang; Song, Xiaoyu; Yin, Xiaolei; Chen, Jianguo; Ding, Mei; Deng, Hongkui

doi:10.1016/j.bbrc.2004.07.060

Cited by 105 publications

(126 citation statements)

References 27 publications

(31 reference statements)

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“…It has been shown that SARS-CoV uses ACE-II (angiotensinconverting enzyme 2) as the cellular receptor [18,19]. A good correlation between the expression of ACE-II and tissue tropism has been shown [20]; however, the presence of ACE-II is unlikely to be the sole determinant for tropism [21]. The C-type lectin CD209L (L-SIGN) human cellular glycoprotein may also possibly be a receptor for SARS-CoV [22].…”

Section: The Virusmentioning

confidence: 96%

“…Haematological disturbances have been suspected to be a result of both direct viral and immune-mediated mechanisms affecting haematopoiesis [16]. The S protein may be the main factor in determining the severity of clinical disease, because of its roles in viral entry, pathogenesis, antiviral response, virulence and cellular and species tropism [8,20,45,79]. Again, studies on animal coronavirus S proteins have helped to define this.…”

Section: Pathogenesismentioning

confidence: 97%

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SARS: clinical presentation, transmission, pathogenesis and treatment options

2006

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SARS (severe acute respiratory syndrome) appeared as the first emerging infectious disease of this century. It is fortunate that the culprit virus can be grown without much difficulty from a commonly used cell line, allowing an unlimited supply of isolates for further molecular studies and leading to the development of sensitive diagnostic assays. How the virus has successfully jumped the species barrier is still a mystery. The superspreading events that occurred within hospital, hotel and high-density housing estate opens a new chapter in the mechanisms and routes of virus transmission. The old practice of quarantine proved to be still useful in controlling the global outbreak. Despite all the available sophisticated tests, alertness with early recognition by healthcare workers and prompt isolation of suspected cases is still the most important step for containing the spread of the infection. Although the rapidly evolving outbreak did not allow the conducting of systematic clinical trails to evaluate treatment options, the accumulated experience on managing SARS patients will improve the clinical outcome should SARS return. Although SARS led to more than 700 deaths worldwide, the lessons learnt have prepared healthcare systems worldwide to face future emerging and re-emerging infections.

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Section: The Virusmentioning

confidence: 96%

Section: Pathogenesismentioning

confidence: 97%

SARS: clinical presentation, transmission, pathogenesis and treatment options

2006

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“…Thus, Huh-7 and 293T cells are permissive to both NL63-and SARS-CoV-S-driven infection (13,16,18) and express the SARS-CoV receptor ACE2 (20,(23)(24)(25), whereas CEMx174, HeLa, and HOS cells are not permissive (13,16,18) and do not express ACE2 (20,25). We therefore determined whether ACE2 plays a role in HCoV-NL63 infection.…”

Section: Hcov-nl63 Engages Ace2 As a Receptor For Infectious Cellularmentioning

confidence: 99%

Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry

Hofmann

Pyrć

Hoek

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

745

699

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Coronavirus (CoV) infection of humans is usually not associated with severe disease. However, discovery of the severe acute respiratory syndrome (SARS) CoV revealed that highly pathogenic human CoVs (HCoVs) can evolve. The identification and characterization of new HCoVs is, therefore, an important task. Recently, a HCoV termed NL63 was discovered in patients with respiratory tract illness. Here, cell tropism and receptor usage of HCoV-NL63 were analyzed. The NL63 spike (S) protein mediated infection of different target cells compared with the closely related 229E-S protein but facilitated entry into cells known to be permissive to SARS-CoV-S-driven infection. An analysis of receptor engagement revealed that NL63-S binds angiotensin-converting enzyme (ACE) 2, the receptor for SARS-CoV, and HCoV-NL63 uses ACE2 as a receptor for infection of target cells. Potent neutralizing activity directed against NL63-but not 229E-S protein was detected in virtually all sera from patients 8 years of age or older, suggesting that HCoV-NL63 infection of humans is common and usually acquired during childhood. Here, we show that SARS-CoV shares its receptor ACE2 with HCoV-NL63. Because the two viruses differ dramatically in their ability to induce disease, analysis of HCoV-NL63 might unravel pathogenicity factors in SARS-CoV. The frequent HCoV-NL63 infection of humans suggests that highly pathogenic variants have ample opportunity to evolve, underlining the need for vaccines against HCoVs.C oronaviruses (CoVs) are enveloped RNA viruses that are grouped according to genome sequence and serology (1). Human CoVs (HCoVs) 229E and OC43 are members of groups I and II, respectively, and infection with these viruses is thought to be responsible for Ϸ30% of common-cold cases (1). In contrast, infection with severe acute respiratory syndrome (SARS)-CoV causes a severe respiratory tract illness (RTI) that is fatal in Ϸ10% of infected individuals (2, 3). The factors that determine the pathogenicity of CoVs are incompletely understood; however, a role for the spike (S) protein has been suggested (4). The S proteins of CoVs, which provide virions with a corona-like appearance, mediate infection of target cells and play a central role in viral replication (4). The interaction of CoV S proteins with specific cellular receptors determines, to a large extent, which cells can be infected (5), and the entry process is an attractive target for antiviral therapy (6).Recently, a HCoV termed NL63 was discovered in infants and immunocompromised adults with RTI (7, 8). HCoV-NL63 is a group I CoV and is most closely related to HCoV-229E (7-9). HCoV-229E employs CD13 (aminopeptidase N) as a receptor for infection of target cells (10,11). Because the NL63-and 229E-S proteins share 56% amino acid identity (7), it is conceivable that HCoV-NL63 also engages CD13 for infectious cellular entry. However, the HCoV-NL63-S protein contains a unique, 179-aa sequence at its N terminus that does not share homology with other known CoV proteins and that might alter the re...

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“…because of the high level of GFP expression in the VSVDG* system (Ogino et al, 2003). In contrast, the time required for infection in the pseudotype retrovirus system is 48 h (Moore et al, 2004;Nie et al, 2004), which is similar to the time required for SARS-CoV to replicate to a level that results in plaque-forming or cytopathic effects in infected cells. To date, there have been no reports of VSV pseudotyped with the S protein of a coronavirus.…”

mentioning

confidence: 95%

“…The SARS-CoV-S protein has a 13 aa signal peptide at its N terminus, a single ectodomain of 1182 aa and a transmembrane region followed by a cytoplasmic domain of 28 aa (Marra et al, 2003;Rota et al, 2003). Recently, pseudotyped retroviruses bearing SARS-CoV-S protein have been generated by several laboratories (Hofmann et al, 2004;Nie et al, 2004;Simmons et al, 2004). It has been shown that these pseudotyped viruses have a cell tropism identical to SARS-CoV and that their infection is dependent on a receptor molecule, angiotensin-converting enzyme 2 (ACE2), indicating that infection is mediated solely by SARS-CoV-S protein.…”

mentioning

confidence: 99%

Vesicular stomatitis virus pseudotyped with severe acute respiratory syndrome coronavirus spike protein

Fukushi

Mizutani

Saijo

et al. 2005

Journal of General Virology

143

124

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Severe acute respiratory syndrome coronavirus (SARS-CoV) contains a single spike (S) protein, which binds to its receptor, angiotensin-converting enzyme 2 (ACE2), induces membrane fusion and serves as a neutralizing antigen. A SARS-CoV-S protein-bearing vesicular stomatitis virus (VSV) pseudotype using the VSVDG* system was generated. Partial deletion of the SARS-CoV-S protein cytoplasmic domain allowed efficient incorporation into VSV particles and led to the generation of a pseudotype (VSV-SARS-St19) at high titre. Green fluorescent protein expression was demonstrated as early as 7 h after infection of Vero E6 cells with VSV-SARS-St19. VSV-SARS-St19 was neutralized by anti-SARS-CoV antibody and soluble ACE2, and its infection was blocked by treatment of Vero E6 cells with anti-ACE2 antibody. These results indicated that VSV-SARS-St19 infection is mediated by SARS-CoV-S protein in an ACE2-dependent manner. VSV-SARS-St19 will be useful for analysing the function of SARS-CoV-S protein and for developing rapid methods of detecting neutralizing antibodies specific for SARS-CoV infection.Severe acute respiratory syndrome (SARS) is a recently described infectious disease caused by a newly identified coronavirus, SARS-CoV (Drosten et al., 2003;Ksiazek et al., 2003). With a mortality rate of over 9 %, SARS has had major health and socio-economic impacts (Fouchier et al., 2003). Despite intensive efforts, no effective antiviral treatments against SARS have yet been established. Studies of SARS-CoV infection have been limited because of the highly infectious nature of the virus and the problem of recent cases in which infection was suspected to have occurred in research laboratories.Entry of SARS-CoV into susceptible cells is mediated by binding of the viral spike (S) protein to receptor molecules. The SARS-CoV-S protein has a 13 aa signal peptide at its N terminus, a single ectodomain of 1182 aa and a transmembrane region followed by a cytoplasmic domain of 28 aa (Marra et al., 2003;Rota et al., 2003). Recently, pseudotyped retroviruses bearing SARS-CoV-S protein have been generated by several laboratories (Hofmann et al., 2004;Nie et al., 2004;Simmons et al., 2004). It has been shown that these pseudotyped viruses have a cell tropism identical to SARS-CoV and that their infection is dependent on a receptor molecule, angiotensin-converting enzyme 2 (ACE2), indicating that infection is mediated solely by SARS-CoV-S protein. Pseudotyped viruses provide a safe viral entry model because of their inability to produce infectious progeny virus. A quantitative assay of pseudotyped virus infection could facilitate research on SARS-CoV entry, cell tropism and neutralizing antibodies. Interestingly, it was reported that a pseudotyped retrovirus bearing a SARS-CoV-S protein variant with a truncation in the cytoplasmic domain was incorporated more efficiently into retrovirus particles than the full-length S protein (Giroglou et al., 2004;Moore et al., 2004).Another pseudotyping system with a vesicular stomatitis virus (VSV) particl...

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Highly infectious SARS-CoV pseudotyped virus reveals the cell tropism and its correlation with receptor expression

Cited by 105 publications

References 27 publications

SARS: clinical presentation, transmission, pathogenesis and treatment options

SARS: clinical presentation, transmission, pathogenesis and treatment options

Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry

Vesicular stomatitis virus pseudotyped with severe acute respiratory syndrome coronavirus spike protein

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