Severe Acute Respiratory Syndrome Coronavirus Phylogeny: toward Consensus

Abstract

Since the identification of a new coronavirus (severe acute respiratory syndrome coronavirus [SARS-CoV]) as the causative agent of the SARS epidemic in the winter of 2002-2003, the origin of the novel agent has remained a hotly debated topic.Which virus was the immediate ancestor of SARS-CoV, and what are the relationships between SARS-CoV and other previously described coronaviruses?Correct answers to these two questions are vital, as substantiated below, for designing strategies to detect, contain, and combat new outbreaks and for dissecting the fundamentals of the SARS-CoV life cycle.Major efforts have been invested in a thus far unsuccessful search for a natural SARS-CoV reservoir.In the meantime, and more outside the spotlight, SARS-CoV genome sequences have been used to define the phylogenetic position of SARS-CoV among coronaviruses.These studies have resulted in a lot of controversy whose intricacies may not be very clear to outsiders.Our purpose is to clarify the situation from an insider's point of view.Originally, coronaviruses were classified on the basis of antigenic cross-reactivity, and in this manner three antigenic groups (1 to 3) were recognized (14).When coronavirus genome sequences began to accumulate, the same groups were evident from phylogenetic analyses of the four structural proteins, N, M, E, and S (19), and of different regions of the giant replicase (3,22).Group boundaries were also supported by the diversity of small open reading frames (ORFs) encoding accessory proteins, which are dispersed among the structural protein genes in the 3Ј-proximal region of the genome (Fig. 1).In the middle of the nineties, a first discord between the antigenicity-based and phylogenetic classifications emerged upon the characterization of the coronavirus porcine epidemic diarrhea virus (PEDV) and human coronavirus 229E (HCoV-229E), one of the common cold viruses.These viruses proved not to have antigenic cross-reactivity with members of the established groups ( 18), yet on the basis of sequence comparisons it was concluded that they segregate into group 1, although they are somewhat separated from porcine transmissible gastroenteritis virus and closely related viruses (subgroup 1b and subgroup 1a, respectively, in Fig. 2) (9).The PEDV and HCoV-229E genomes also share an ORF specific for group 1