Coronavirus HKU1 Infection in the United States

Frank Esper; Carla Weibel; David Ferguson; Marie L. Landry; Jeffrey S. Kahn


Emerging Infectious Diseases. 2006;12(4) 

In This Article

Abstract and Introduction


In 2005, a new human coronavirus, HCoV-HKU1, was identified in Hong Kong. We screened respiratory specimens collected from December 16, 2001, to December 15, 2002, from children <5 years of age who tested negative for respiratory syncytial virus, parainfluenza viruses, influenza virus, and adenovirus for HCoV-HKU1 by reverse transcription–polymerase chain reaction. Overall, 1,048 respiratory specimens from 851 children were tested, and 9 HCoV-HKU1–positive children (1%) were identified, 2 of whom had 2 positive specimens. Children who had HCoV-HKU1 infection had evidence of either upper or lower respiratory tract infection or both. Two patients had disease beyond the respiratory tract. HCoV-HKU1 was identified from December 2001 to February 2002. Sequence analyses suggest that a single strain was circulating. HCoV-HKU1 is therefore likely circulating in the United States and is associated with upper and lower respiratory tract disease.


Lower respiratory tract disease accounts for ≈4 million deaths annually worldwide.[1] Viruses such as influenza virus, respiratory syncytial virus (RSV), and parainfluenza viruses are responsible for much of this respiratory tract infection. However, in a substantial proportion of respiratory tract disease, no pathogen is identified.[2]

Coronaviruses (CoV) infect a wide variety of mammals and birds, causing disease of the respiratory tract, gastrointestinal tract, and central nervous system. These viruses may be transmitted from species to species.[3] In humans, CoV have been associated with community-acquired upper respiratory tract infections.[4] Human CoV (HCoV) have also been implicated in outbreaks of diarrhea as well as in demyelinating disorders of the central nervous system, though these data are controversial.[5,6] The study and identification of HCoV have been hampered by the difficulty in propagating these viruses in vitro.

The identification of the severe acute respiratory syndrome–associated CoV in 2003 sparked renewed interest in the study of HCoV,[7] and 4 previously unidentified HCoV have subsequently been discovered. HCoV-NL63, HCoV-NL, and the New Haven coronavirus (HCoV-NH) are closely related group I CoV and likely represent strains of the same species of virus.[8,9,10] HCoV-NL63 and HCoV-NL were originally identified by cell culture techniques, while HCoV-NH was discovered by using broadly reactive CoV molecular probes. These related viruses were identified in both children and adults with respiratory tract disease. HCoV-NH was found in 8.8% of children <5 years of age whose specimens originally tested negative for RSV, influenza virus, parainfluenza viruses, and adenoviruses.[10] Furthermore, these newly discovered viruses may be the cause of disease beyond the respiratory tract. In a case-control study, HCoV-NH was found to be associated with Kawasaki disease,[11] although these data are controversial.[12,13]

In 2005, Woo et al. reported a novel group II CoV, designated HCoV-HKU1, from a 71-year-old man with pneumonia[14] who had recently returned to Hong Kong from the Shenzhen, China. As in the discovery of HCoV-NH,[10] this virus was detected with molecular probes. Although growth of HCoV-HKU1 in multiple cell lines was unsuccessful, the complete genomic sequence was obtained. Phylogenetic analysis showed that this new group II CoV is most closely related to the mouse hepatitis virus and is distinct from HCoV-OC43, the only other known group II HCoV. Screening of 400 nasopharyngeal aspirates by reverse transcription–polymerase chain reaction (RT-PCR) with HCoV-HKU1–specific primers showed 1 other HCoV-HKU1 isolate from a 35-year-old woman with pneumonia. After the original report, HCoV-HKU1 was identified in 10 patients in northern Australia.[15] Respiratory samples were collected between May and August (winter in Australia) and screened by RT-PCR with both nonspecific CoV and specific HKU1 primers. Most HCoV-HKU1–positive samples originated from children in the later winter months. However, the seasonal and geographic distribution of this virus is still unclear. To address these issues, we sought to determine whether HCoV-HKU1 circulated in New Haven, Connecticut, and to define clinical characteristics associated with HCoV-HKU1 infection in infants and children.


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