A previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans

Abstract

Respiratory infections constitute the most widespread human infectious disease, and a substantial proportion of them are caused by unknown etiological agents. Reoviruses (respiratory enteric orphan viruses) were first isolated from humans in the early 1950s and so named because they were not associated with any known disease. Here, we report a previously unknown reovirus (named "Melaka virus") isolated from a 39-year-old male patient in Melaka, Malaysia, who was suffering from high fever and acute respiratory disease at the time of virus isolation. Two of his family members developed similar symptoms approximately 1 week later and had serological evidence of infection with the same virus. Epidemiological tracing revealed that the family was exposed to a bat in the house approximately 1 week before the onset of the father's clinical symptoms. Genome sequence analysis indicated a close genetic relationship between Melaka virus and Pulau virus, a reovirus isolated in 1999 from fruit bats in Tioman Island, Malaysia. Screening of sera collected from human volunteers on the island revealed that 14 of 109 (13%) were positive for both Pulau and Melaka viruses. This is the first report of an orthoreovirus in association with acute human respiratory diseases. Melaka virus is serologically not related to the different types of mammalian reoviruses that were known to infect humans asymptomatically. These data indicate that bat-borne reoviruses can be transmitted to and cause clinical diseases in humans.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Syncytia formation in MelV-infected MDCK cells. (A) Mock-infected. (B) MelV-infected. Two types of syncytial cells were observed: cells still attached to culture flask surface (filled arrows) and cells detaching from the surface (open arrows).

Fig. 2.

Electron micrographs of MelV. (A) Negative-stained MelV. (Scale bar: 200 nm.) (B) Image of an ultrathin section of a MelV-infected multinucleated Vero cell. N, nucleus; arrows, paracrystalline viral arrays (inclusion bodies not shown). (Scale bar: 5 μm.) (C) Higher magnification view of a paracrystalline array. (Scale bar: 200 nm.)

Fig. 3.

Comparison of genome segments and coding strategy of the polycistronic S-class genome segments. (A) Genome segments of MelV and PulV separated on a 1% agarose gel. (B) Genome segments of MelV and PulV separated on a 10% SDS-polyacrylamide gel. The classes of genome segments (L, large; M, medium; S, small) are labeled on the left, and the asterisks indicate comigrating bands where more than one segment is present. (C) Coding arrangement of the polycistronic S segments of three bat orthoreoviruses in comparison with two other mammalian orthoreovirus species. The line on top represents the RNA genome and the shaded boxes underneath depicture protein-coding regions in reading frames 1–3 (top to bottom). Numbers refer to size, in base pairs, of the genome segments and to the first and last nucleotides of the individual ORFs (excluding the stop codons). The names of the encoded proteins are indicated within the shaded boxes.

Fig. 4.

Phylogenetic trees of orthoreoviruses based on deduced amino acid sequence of the major inner (A) and outer (B) capsid proteins. The GenBank accession number for each sequence is given in bracket next to the abbreviated virus name. ARV, avian reovirus; BRV, baboon reovirus; RRV, reptilian reovirus. Numbers at nodes indicate levels of bootstrap support calculated from 1,000 trees.