The New Age of Virus Discovery: Genomic Analysis of a Novel Human Betacoronavirus Isolated from a Fatal Case of Pneumonia

Holmes, Kathryn V.; Dominguez, Samuel R.

What questions must be answered to show whether HCoV-EMC is likely to cause an epidemic or adapt to become endemic in humans? First, it is necessary to prove whether the HCoV-EMC cultured from the first patient actually caused his fatal disease (7) . Several bacterial pathogens were also cultured from his respiratory tract, although this is not uncommon in severely ill patients on respirators. Development of an animal model for HCoVinduced respiratory disease would fulfill Koch's postulates and be useful for testing candidate coronavirus drugs and vaccine strategies. Sera from humans in the Middle East and elsewhere are being tested by ELISA for HCoV-EMC-specific antibodies to determine the prevalence of infection of humans in different regions and estimate the percentage of clinically apparent HCoV-EMC infections and the case/fatality ratio. Surveillance of bats and other animals in the Middle East and elsewhere for the presence of RNA from betacoronavirus lineage c viruses or antibodies to these viruses will help to identify reservoir hosts and possible intermediate hosts that could transmit the virus to humans. So far, no epidemiological connections have been found between animals and the HCoV-EMC patients. This virus is apparently much less easily transmitted from human to human than SARS-CoV, although three of the cases in Saudi Arabia were within one family and several health care workers who cared for two of the confirmed cases in Jordan also developed pneumonia and are now considered probable cases (5) . It is possible that as the virus replicates in sporadic cases, mutations, particularly in the genes encoding the spike protein and any immunomodulatory proteins, might be selected that increase human-to-human transmissibility. Sporadic HCoV-EMC infections in epidemiologically unlinked individuals in the Middle East suggest that it is a zoonotic virus. Where encounters between humans and wildlife have become common, sporadic zoonotic infections may occur without human-to-human transmission. This so-called "virus chatter" was obvious in retrospective studies of SARS-CoV infections in China which showed that isolated cases occurred well before the virus began to spread from human to human during the SARS pandemic (8) (9) (10) . Mutations in the SARS-CoV spike protein and other viral proteins were associated with the transition from "chatter" to epidemic. It is possible that HCoV-EMC is not yet a human-adapted virus and has simply been detected in rare cases of "chatter" by increasingly sophisticated surveillance. The work by van Boheemen et al. demonstrates the ability of state-of-the-art technology and bioinformatics to obtain full-genome sequence data within days and provide critical insight into the potential risks associated with novel viral pathogens (6) . Over the past decade, other advances, including the development of enhanced virus detection technologies, surveillance programs, increased global awareness and communication through Internet-based technologies such as ProMed, real-time sharing of genome sequences in GenBank, and Internet-based publications and the posting of publications in advance of printing, as well as increasing collaborations between researchers and medical and veterinary practitioners such as the One Health Initiative, have greatly facilitated rapid and effective responses to threats of new emerging infectious diseases.