808 JID 2006:194 (15 September) Tang et al. M A J O R A R T I C L E The Large 386-nt Deletion in SARS-Associated Coronavirus: Evidence for Quasispecies? Julian W. Tang,1Jo L. K. Cheung,1Ida M. T. Chu,1Joseph J. Y. Sung,2,3Malik Peiris,4and Paul K. S. Chan1,3 Departments of 1Microbiology and2Medicine and Therapeutics, Centre for Emerging Infectious Diseases, and3School of Public Health, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, and 4Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China The severe acute respiratory syndromeassociated coronavirus (SARS-CoV) is reported to have deletions of various sizes. Recently, the large 386-nucleotide deletion (L386del) comprising nucleotide positions 27719- 28104 and spanning open reading frames 911 has been reported in the genomes of some human isolates from Hong Kong. In this study, archived specimens from 71 patients with SARS who were admitted to the New Territory East Cluster Hospitals in Hong Kong were analyzed to determine whether the L386del variant of SARS-CoV was present. There was no clear relationship between the presence of the L386del variant and SARS clinical severity as defi ned either by the need for intensive-care therapy and/or ventilation or by death. One patient had evidence of both the L386del variant and the wild-type variant in the same clinical specimen, supporting the idea that SARS-CoV exists as a quasispecies in some patients, although the clinical signifi cance of these quasispecies remains unclear. Since the worldwide SARS epidemic in 2003, many studies have focused on the genomics of the SARS- associatedcoronavirus(SARS-CoV),tounderstandmore about the pathogenic potential of this new pathogen. Several signifi cant differences betweenthevariousSARS- CoV isolates from different patients and animal hosts have now been identifi ed. Guan et al. 1 found that the majority of human SARS-CoV associated with the epi- demichada29-ntdeletionspanningopenreadingframes (ORFs) 10 and 11 (in Guan et al.s original nomencla- ture), compared with the SARS-like coronavirus (SL- CoV) identifi ed in Himalayan palm civet cats (Paguma larvata) from a Guangdong live-animal market; this 29- nt deletion in the human SARS-CoV genome comprised nucleotide positions (np) 2786927897 when that ge- Received 28 March 2006; accepted 10 May 2006; electronically published 11 August 2006. Potential confl icts of interest: none reported. Financial support: Research Grants Council of the Hong Kong Special Ad- ministrative Region, China (project HKU7542/03M). Reprints or correspondence: Prof. Paul K. S. Chan, Dept. of Microbiology, The Chinese University of Hong Kong, 1/F Clinical Science Bldg., Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR (paulkschancuhk.edu.hk). The Journal of Infectious Diseases2006;194:80813 ? 2006 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2006/19406-0013$15.00 nome was aligned with the TOR-2 SARS-CoV reference sequence (GenBank accessionno.NC004718).Thefunc- tional signifi canceofthisdeletionisuncertain,although it may represent an adaptive mutation to a human host by SARS-CoV from a potential civet-cat animal res- ervoir 1, 2. However, it has been reported that the human-adapted SARS-CoV with the 29-nt deletion re- mains just as able to infect the civet cat 3. Other studies have suggested that bats may be an alternative animal reservoir for SARS-CoV 4, 5, which suggests that the civet cat is a secondary, amplifying host for SARS-CoV rather than the primary reservoir. The bat SL-CoV also has the additional 29 nt in ORFs 10 and 11 and, in this respect, is similar to the civet-cat SL- CoV 4, 5. Most recently, experiments haveshownthat replacement of this 29-nt deletion does not alter the in vitro or in vivo replication, persistence, or duration of the viral load in the murine model, although this fi nd- ing does not exclude the possibility that there could be more-dramatic effects if a civet-cat or raccoon-dog model were used 6. Other deletions have been noted in other areas of the SARS-CoV genome. An 82-nt deletion in ORF 8 has been reported in a study 7 whose authors also suggested that the earliest phase of the SARS epidemic by guest on April 12, 2016http:/jid.oxfordjournals.org/Downloaded from Large SARS-CoV Genomic Deletion JID 2006:194 (15 September) 809 Figure 1.Location, in the SARS-associated coronavirus genome, of the large 386-nt deletion (L386del), in relation to open reading frames (ORFs) 911. PCR, polymerase chain reaction. (N.B.: the sizes of the bars are for illustrative purposes only and are not to scale.) (i.e., when SARS was confi ned to China) were characterized by 2 major SARS-CoV genotypes, one of them characterized by the 29-nt deletion and the other harboring the 82-nt deletion. These 2 genotypes had also been isolated from animals in Guangdong and other provinces (e.g., Hubei) in China. The aut