High Secretion of Interferons by Human Plasmacytoid Dendritic Cells upon Recognition of Middle East Respiratory Syndrome Coronavirus

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV In 2012 a novel human betacoronavirus associated with severe respiratory disease emerged in Saudi Arabia (1). Due to its geographic distribution, this new virus was classified as Middle East respiratory syndrome coronavirus (MERS-CoV) (2). MERS-CoV is associated with high fatality rates (3, 4), and case numbers globally have increased to 909 laboratory-confirmed cases with 331 fatalities (as of 21 November 2014 [http://www.who.int/csr/don/ 21-november-2014-mers/en/]). In parallel, the geographic distribution has expanded (4). MERS-CoV is the second emerging CoV with severe pathogenicity in humans within 10 years after the severe acute respiratory syndrome coronavirus (SARS-CoV) that infected approximately 8,000 people worldwide during its spread in 2003 (5). Human-to-human transmissions have been reported for MERS-CoV, but transmissibility seems to be inefficient (6, 7). MERS-CoV persists in animal reservoirs, i.e., dromedary camels (8), and transmission events between camels and contact persons have been reported (7-10). Thus, MERS-CoV infection of men has zoonotic origins, similar to SARS-CoV, but unlike SARS-CoV, where bats have been identified as the original virus reservoir, bats have been reported to host only closely related viruses of MERSCoV (11). However, the only small-animal model developed so far involves type I interferon receptor (IFNAR)-deficient mice expressing human dipeptidyl peptidase 4 (huDPP4; CD26), the entry receptor of MERS-CoV (12), in the lung after intranasal administration of huDPP4-expressing adenoviral vectors (13). MERS-CoV causes symptoms in humans similar to those of SARS-CoV infection, such as severe pneumonia with acute respi-

Co‐localization of Middle East respiratory syndrome coronavirus ( MERS ‐CoV) and dipeptidyl peptidase‐4 in the respiratory tract and lymphoid tissues of pigs and llamas

“…MERS‐CoV has been reported to productively infect human DCs in vitro , which can also serve as a vector for viral dissemination within the body (Chu et al., ). However, human DCs can secrete interferons (IFNs) and then trigger a potent innate/adaptive response upon MERS‐CoV infection (Scheuplein et al., ). Thus, those DC‐like cells could interfere with viral replication by releasing cytokines, like type I IFNs, or delivering antigens to other immune cells at the time MERS‐CoV reaches this area (Scheuplein et al., ).…”

“…However, human DCs can secrete interferons (IFNs) and then trigger a potent innate/adaptive response upon MERS‐CoV infection (Scheuplein et al., ). Thus, those DC‐like cells could interfere with viral replication by releasing cytokines, like type I IFNs, or delivering antigens to other immune cells at the time MERS‐CoV reaches this area (Scheuplein et al., ). Future studies on this topic are therefore required to verify whether these cells are effectively DCs and if they are able to express DPP4 at the surface before infection.…”

Camelid type I interferons: Identification and functional characterization of interferon alpha from the dromedary camel (Camelus dromedarius)

“…Dromedary camels are also reported to be the reservoir of another major zoonotic diseasethe Middle East Respiratory Syndrome coronavirus (MERS-CoV) and as a direct source of infection to humans (Gossner et al, 2016;Wernery et al, 2017).Type I interferons play an important role in the host response against MERS-CoV. Interaction of the MERS-CoV with the human antigen-presenting cells (APCs) and dendritic cells significantly induce the expression of type I and III IFNs, particularly IFN-α (Scheuplein et al, 2015). IFN-α2b treatment along with ribavirin is effective in treating MERS-CoV (Falzarano et al, 2013).…”

Characteristics of Traveler with Middle East Respiratory Syndrome, China, 2015

“…However, a previous study also showed increased levels of interferon-α in a patient who survived MERS-CoV infection but not in a person who died of MERS ( 7 ). Although MERS-CoV evades induction of innate immune responses by cell types, the virus elicits interferon responses in plasmacytoid dendritic cells in vitro ( 8 ). Levels of tumor necrosis factor-α, MIP-1α, MIP-1β, IL-10, and IL-1β did not increase in any of these specimens.…”