Discovery of a novel polyomavirus in acute diarrheal samples from children

Abstract

Polyomaviruses are small circular DNA viruses associated with chronic infections and tumors in both human and animal hosts. Using an unbiased deep sequencing approach, we identified a novel, highly divergent polyomavirus, provisionally named MX polyomavirus (MXPyV), in stool samples from children. The ∼5.0 kB viral genome exhibits little overall homology (<46% amino acid identity) to known polyomaviruses, and, due to phylogenetic variation among its individual proteins, cannot be placed in any existing taxonomic group. PCR-based screening detected MXPyV in 28 of 834 (3.4%) fecal samples collected from California, Mexico, and Chile, and 1 of 136 (0.74%) of respiratory samples from Mexico, but not in blood or urine samples from immunocompromised patients. By quantitative PCR, the measured titers of MXPyV in human stool at 10% (weight/volume) were as high as 15,075 copies. No association was found between the presence of MXPyV and diarrhea, although girls were more likely to shed MXPyV in the stool than boys (p=0.012). In one child, viral shedding was observed in two stools obtained 91 days apart, raising the possibility of chronic infection by MXPyV. A multiple sequence alignment revealed that MXPyV is a closely related variant of the recently reported MWPyV and HPyV10 polyomaviruses. Further studies will be important to determine the association, if any, of MXPyV with disease in humans.

Figure 1. Genome organization of MXPyV.

The 4,939-nt circular genome of MXPyV (A) contains putative coding regions for VP1, VP2, VP3, ST-Ag, and LT-Ag (yellow arrows). C1, C2, and C3 (gray) denote de novo assembled contigs from deep sequencing data. (B) Domains and binding motifs present in the spliced LT-Ag and ST-Ag of MXPyV.

Figure 2. Amino acid phylogenetic analysis of MXPyV relative to other polyomaviruses.

(A) VP1, (B) VP2, (C) ST-Ag, (D) LT-Ag. Bayesian support levels are indicated at each branching point. Abbreviations: AGM, African green monkey; SV40, simian virus 40; SV12, simian virus 12; SqMPy, squirrel monkey; CaliSeaLion, California sea lion. Other abbreviations and GenBank accession numbers are described in the text. Note that Merkel cell virus (MCV) is not included in the LT-Ag phylogeny due to the presence of truncation mutations.

Figure 3. Amino acid identities of the VP1, VP2, small T-antigen, large T-antigen of MXPyV relative to that of other polyomaviruses.

Figure 4. Whole-genome sequence alignment of MXPyV relative to other recently described gut-associated polyomaviruses HPyV10 and MWPyV.