Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential

Abstract

The recent emergence of a novel human coronavirus (HCoV-EMC) in the Middle East raised considerable concerns, as it is associated with severe acute pneumonia, renal failure, and fatal outcome and thus resembles the clinical presentation of severe acute respiratory syndrome (SARS) observed in 2002 and 2003. Like SARS-CoV, HCoV-EMC is of zoonotic origin and closely related to bat coronaviruses. The human airway epithelium (HAE) represents the entry point and primary target tissue for respiratory viruses and is highly relevant for assessing the zoonotic potential of emerging respiratory viruses, such as HCoV-EMC. Here, we show that pseudostratified HAE cultures derived from different donors are highly permissive to HCoV-EMC infection, and by using reverse transcription (RT)-PCR and RNAseq data, we experimentally determined the identity of seven HCoV-EMC subgenomic mRNAs. Although the HAE cells were readily responsive to type I and type III interferon (IFN), we observed neither a pronounced inflammatory cytokine nor any detectable IFN responses following HCoV-EMC, SARS-CoV, or HCoV-229E infection, suggesting that innate immune evasion mechanisms and putative IFN antagonists of HCoV-EMC are operational in the new host. Importantly, however, we demonstrate that both type I and type III IFN can efficiently reduce HCoV-EMC replication in HAE cultures, providing a possible treatment option in cases of suspected HCoV-EMC infection.

What are our pharmacotherapeutic options for MERS-CoV?

“…Experience from SARS-CoV showed that different regimens of interferon were used alone or in combination with ribavirin [4]. However, both IFN-a and IFN-l inhibited MERS-CoV more effectively than SARS-CoV [27]. In vitro studies also showed that the addition of IFN-b had a significant antiviral effect on MERS-CoV resulting in a 3-log reduction of the virus to undetectable levels [28].…”

Specific serology for emerging human coronaviruses by protein microarray

“…The new coronavirus seems to be fully able to penetrate human bronchial epithelia cultures. At the same time, like SARS-CoV, it appears to be sensitive to treatment with interferons (types I and III) [17]. [13].…”

Middle East Respiratory Syndrome Coronavirus (MERS CoV): An Emerging Pathogen

“…Infection experiments in cell culture showed that MERS-CoV does not use the SARS-CoV receptor, angiotensin converting enzyme 2 (ACE2), for entry, and that MERS-CoV has a much broader host range than the epidemic isolate of SARS-CoV. [8][9][10][11][12][13][14] The genome structure of MERS-CoV is similar to other coronaviruses, with the 52 two-thirds of the genome encoding the non-structural proteins (NSPs) required for viral genome replication, the remaining 32 third of the genome encoding the structural genes that make up the virion (spike, envelope, membrane, and nucleocapsid proteins), and four accessory genes interspersed within the structural gene region. 2 One additional similarity between MERS-CoV and SARS-CoV is their abilities to inhibit a robust type I interferon (IFN) response in infected cells.…”

“…Importantly, several studies show that MERS-CoV, similar to SARS-CoV, does not induce an early type I IFN response, suggesting that MERS-CoV may encode proteins that inhibit sensing of the viral RNA during infection. 8,11,14,15 The modulation of these pathways may explain the increased lethality of MERSCoV.…”