The Middle East Respiratory Syndrome—How Worried Should We Be?

Perlman, Stanley

Remarkably, the identity of the MERS-CoV receptor, dipeptidyl peptidase 4 (DDP4), was published only 6 months after the virus was first reported in the literature (10) . Both bat and human DPP4 sensitize resistant cells for infection, supporting the notion that virus could cross species from bats to infect humans (5) . DPP4, the receptor, is an ectopeptidase. Similar molecules are also used by other coronaviruses to enter cells, including human angiotensinconverting enzyme 2 (hACE2), which is used by SARS-CoV and HCoV-NL63, and aminopeptidase N (APN), which is used by several alphacoronaviruses. The catalytic sites of hACE2, APN, and likely DPP4 are not required for virus entry (10) . Intriguingly, both hACE2 and DPP4 are shed from the cell surface (11, 12) . Loss of hACE2 results in more severe pulmonary disease, while DPP4 is a neutrophil chemorepellent (13) . Changes in DPP4 shedding that occur as a result of infection with MERS-CoV could influence the composition of the immune cell infiltrate, thereby ultimately affecting the outcome of the infection. DPP4 is also expressed on immune cells, including T cell lymphocytes (12) , and is required for optimal function of these cells, but there is no evidence yet to suggest that MERS-CoV infection of lymphocytes occurs or plays a major role in pathogenesis. Curiously, CEACAM-1, the host cell receptor for mouse hepatitis virus (MHV), a murine coronavirus, is also expressed on T cells and is involved in signaling (14), but MHV does not infect T lymphocytes.