Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus

Zhou, Jie; Li, Cun; Zhao, Guangyu; Chu, Hin; Wang, Dong; Yan, Helen H.N.; Poon, Vincent Kwok-Man; Wen, Lei; Wong, Bosco Ho-Yin; Zhao, Xiaoyu; Chiu, Man Chun; Yang, Dong; Wang, Yixin; Au-Yeung, Rex; Chan, Iris Hiu-Shuen; Sun, Shihui; Chan, Jasper Fuk‐Woo; To, Kelvin Kai‐Wang; Memish, Ziad A.; Corman, Victor M.; Drosten, Christian; Hung, Ivan Fan-Ngai; Zhou, Yusen; Leung, Suet Yi; Yuen, Kwok‐Yung

doi:10.1126/sciadv.aao4966

Cited by 359 publications

(396 citation statements)

References 46 publications

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“…Cellular β‐actin was probed as loading control. Mouse lung slides were used for immunofluorescence staining with anti‐nucleoprotein (NP, Millipore, MAB8257F‐5, 1:1,000 dilution) to label the virus‐infected cells as described elsewhere (Zhou et al , ) and imaged using Carl Zeiss LSM 800 confocal microscopy.…”

Section: Methodsmentioning

confidence: 99%

Identification and characterization of GLDC as host susceptibility gene to severe influenza

et al. 2018

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Glycine decarboxylase (GLDC) was prioritized as a candidate susceptibility gene to severe influenza in humans. The higher expression of GLDC derived from genetic variations may confer a higher risk to H7N9 and severe H1N1 infection. We sought to characterize GLDC as functional susceptibility gene that GLDC may intrinsically regulate antiviral response, thereby impacting viral replication and disease outcome. We demonstrated that GLDC inhibitor AOAA and siRNA depletion boosted IFNβ‐ and IFN‐stimulated genes (ISGs) in combination with PolyI:C stimulation. GLDC inhibition and depletion significantly amplified antiviral response of type I IFNs and ISGs upon viral infection and suppressed the replication of H1N1 and H7N9 viruses. Consistently, GLDC overexpression significantly promoted viral replication due to the attenuated antiviral responses. Moreover, GLDC inhibition in H1N1‐infected BALB/c mice recapitulated the amplified antiviral response and suppressed viral growth. AOAA provided potent protection to the infected mice from lethal infection, comparable to a standard antiviral against influenza viruses. Collectively, GLDC regulates cellular antiviral response and orchestrates viral growth. GLDC is a functional susceptibility gene to severe influenza in humans.

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Section: Methodsmentioning

confidence: 99%

Identification and characterization of GLDC as host susceptibility gene to severe influenza

et al. 2018

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“…After infection of mice transgenic for the expression of the host DPP4 receptor, histological examination showed MERS-CoV enteric infection in all inoculated mice with progression to infection of the lung tissues, indicating the development of sequential respiratory infection. 39 Transmission via contact with contaminated hospital environments is possible during outbreaks, although genomic studies providing an evidence base are lacking. Since environmental contamination is a potential source of infection, it is prudent to take precautionary infection control measures.…”

Section: Epidemiological Patterns Of Human Casesmentioning

confidence: 99%

Middle East respiratory syndrome

et al. 2020

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The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.

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“…Juice adjusted to pH 4 or pH 5 inactivated 99% and 90%, respectively of infectious particles (Witkowski et al, 2017). Likewise, MERS-coronavirus (titer 7.5 × 10 6 ) is completely inactivated after an incubation for 30 min in fasted state simulated gastric fluid (pH 1.6, containing pepsin), but stable in a solution simulating the gastric fluid after food uptake (pH 5, but no pepsin) (Zhou et al, 2017). Taken together, enveloped viruses are apparently rapidly and quantitatively inactivated at a pH below 5.…”

Section: Discussionmentioning

confidence: 99%

Mimicking the passage of avian influenza viruses through the gastrointestinal tract of chickens

Han

Bertzbach

Veit

2019

Veterinary Microbiology

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In contrast to human influenza viruses that replicate in the respiratory tract and are airborne transmitted, avian viruses also replicate in gut epithelial cells and are transmitted via the fecal-oral route. On this route, the virus is exposed to destructive fluids of the digestive tract, which are acidic and contain the proteases pepsin (gizzard) or chymotrypsin and trypsin (intestine). Only the latter enzyme activates virus by cleaving hemagglutinin (HA) into HA 1 and HA 2 subunits.We mimicked the passage of viruses through the gastrointestinal tract by treating them with digestive fluids from chicken and determined titers and integrity of HA by western-blot. Gizzard fluid completely inactivated virions and degrades HA even at a high dilution, but only if the pH was kept acidic. If the fluid is diluted with neutral buffer (mimicking virus uptake with seawater) particles were more resistant. Virions containing an uncleaved HA were even activated suggesting that gastric juice contains a trypsin-like protease. Undiluted intestinal fluid inactivated particles and destroyed HA, but diluted fluid activated virions. A virus isolated from the duck´s intestine is more tolerant against intestinal fluid compared to fowl plague virus suggesting that the former is better adapted to grow in the intestine. We also demonstrate that influenza viruses replicate to high titers in a novel chicken epithelial gut cell line. While viruses with a monobasic HA cleavage site require addition of trypsin, these cells effectively process HA with a polybasic cleavage site, which could be blocked with an inhibitor of the cellular furin protease.

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Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus

Abstract: Human intestinal tract as an alternative route to acquire MERS-CoV infection.

Cited by 359 publications

References 46 publications

Identification and characterization of GLDC as host susceptibility gene to severe influenza

Identification and characterization of GLDC as host susceptibility gene to severe influenza

Middle East respiratory syndrome

Mimicking the passage of avian influenza viruses through the gastrointestinal tract of chickens

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