Novel polyomaviruses in South American bats and their relationship to other members of the family Polyomaviridae

Fagrouch, Zahra; Sarwari, Roya; Lee, Anne; Delaval, Marguerite; Thoisy, Benoı̂t de; Lacoste, Vincent; Verschoor, Ernst J.

doi:10.1099/vir.0.044149-0

Cited by 49 publications

(29 citation statements)

References 28 publications

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“…S5A) or the entire genome (SI Appendix, Fig. S5B) were similar and consistent with recently published phylogenetic analyses of LT genes from polyomaviruses (23)(24)(25). Strikingly, we found that one lineage of polyomaviruses that includes MCPyV and MPyV, as well as other polyomaviruses from primates, raccoons, rodents, bats, and one other human PyV, Trichodysplasia spinulosa-associated polyomavirus (TSPyV), all share the property of potentially encoding an overprinting ALTO/MT-like gene (Fig.…”

Section: Resultssupporting

confidence: 73%

Identification of an overprinting gene in Merkel cell polyomavirus provides evolutionary insight into the birth of viral genes

Carter

Daugherty

Qi³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

152

149

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Many viruses use overprinting (alternate reading frame utilization) as a means to increase protein diversity in genomes severely constrained by size. However, the evolutionary steps that facilitate the de novo generation of a novel protein within an ancestral ORF have remained poorly characterized. Here, we describe the identification of an overprinting gene, expressed from an Alternate frame of the Large T Open reading frame (ALTO) in the early region of Merkel cell polyomavirus (MCPyV), the causative agent of most Merkel cell carcinomas. ALTO is expressed during, but not required for, replication of the MCPyV genome. Phylogenetic analysis reveals that ALTO is evolutionarily related to the middle T antigen of murine polyomavirus despite almost no sequence similarity. ALTO/MT arose de novo by overprinting of the second exon of T antigen in the common ancestor of a large clade of mammalian polyomaviruses. Taking advantage of the low evolutionary divergence and diverse sampling of polyomaviruses, we propose evolutionary transitions that likely gave birth to this protein. We suggest that two highly constrained regions of the large T antigen ORF provided a start codon and C-terminal hydrophobic motif necessary for cellular localization of ALTO. These two key features, together with stochastic erasure of intervening stop codons, resulted in a unique protein-coding capacity that has been preserved ever since its birth. Our study not only reveals a previously undefined protein encoded by several polyomaviruses including MCPyV, but also provides insight into de novo protein evolution. gene evolution | synonymous substitution | disordered motifs T he birth of new genes has fascinated biologists for decades. Although the steps required to generate a new gene by gene duplication or gene rearrangement have been characterized, less is known about the birth of new genes de novo. One particularly intriguing mechanism of de novo gene birth is via "overprinting," in which a novel overprinting gene is encoded as an alternate ORF within an ancestral "overprinted" gene (1). Overprinting results in two unrelated functional proteins encoded as overlapping ORFs within the same DNA sequence. However, the origins of such a complex evolutionary solution have remained elusive.Viruses appear to be especially adept at this form of evolutionary innovation. This frequent use of overprinting is likely the result of the severe constraints imposed on viral genome size, making gene innovation more likely to occur as overprinting rather than within a noncoding region (2). Due to the numerous examples of overprinting in single-stranded RNA viruses, a great deal of research has focused in particular on this class of viruses (3-6). However, small DNA viruses, such as adenoviruses, papillomaviruses, and polyomaviruses, have a similar requirement to maximize the coding capacity of their genomes. In this study, we have taken advantage of our identification of an overprinting gene born in the ancestor of a large clade of polyomaviruses to investigate the...

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Section: Resultssupporting

confidence: 73%

Identification of an overprinting gene in Merkel cell polyomavirus provides evolutionary insight into the birth of viral genes

Carter

Daugherty

Qi³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

152

149

View full text Add to dashboard Cite

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“…All digital control sequences ‘spiked’ into the data sets prior to bioinformatic analysis could be recovered correctly by both ways of data analysis, DTS and reference mapping. At the nucleotide level, the lowest homology hits matched a recently discovered bat polyomavirus [JQ958891.1 ] and Pan troglodytes verus polyomavirus (HQ385746.1). At the protein level, the hit with the weakest homology recovered was Gorilla gorilla gorilla polyomavirus (ADQ54205.1).…”

Section: Resultsmentioning

confidence: 93%

No human virus sequences detected by next‐generation sequencing in benign verrucous skin tumors occurring in BRAF‐inhibitor‐treated patients

Ganzenmueller

Hage

Yakushko

et al. 2013

Experimental Dermatology

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Patients treated with BRAF inhibitors (e.g. vemurafenib), a novel targeted therapy for advanced melanoma harbouring certain BRAF mutations, develop numerous adverse cutaneous side effects, including skin tumors such as squamous cell carcinoma or non-malignant verruciform keratinocyte proliferations, termed 'BRAF-inhibitor-associated verrucous keratosis (BAVK) lesions'. These keratinocyte proliferations are believed to be caused by paradoxical hyperactivation of the MAPK pathway in cells with wild-type BRAF, but mutated RAS. However, due to the clinical and histological verruca-like appearance of these lesions, additional aetiologic cofactors, such as infectious agents (i.e. oncogenic viruses), might be suspected. Therefore, we performed 454 high-throughput sequencing of BAVK lesions from vemurafenib-treated patients on the transcript level to identify actively transcribed viral sequences of known [e.g. human papilloma viruses (HPV)] or even yet-unknown viruses. Next-generation sequencing did not identify transcripts of any human viruses out of 1 595 161 reads obtained from BAVK lesions of four patients. Nevertheless, all controls were recognized correctly, and the detection of sequences derived from the cutaneous microbiome (e.g. skin commensals and bacterial phages) confirmed the validity and sensitivity of the sequencing data. Our results are consistent with preliminary histological and immunohistochemical findings recently reported by others, who also failed to detect the expression of HPV proteins in BAVK. Although the patient number is limited and we cannot exclude the possibility of having missed a viral transcript of very low abundance, our study argues against a viral aetiology of BRAF-inhibitor-associated verruciform keratoses occurring under vemurafenib.

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“…The focus on zoonotic RNA viruses has led to slower developments in understanding interactions between the bat immune system and DNA viruses. Multiple DNA viruses have been detected in bats, including herpesviruses (77-80), adenoviruses (81), hepadnaviruses (82), poxviruses (83) and polyomaviruses (81,84,85). These discoveries highlight the need to study antiviral responses to DNA viruses in bats.…”

Section: Sensing Dna Virusesmentioning

confidence: 99%

Novel Insights Into Immune Systems of Bats

et al. 2020

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In recent years, viruses similar to those that cause serious disease in humans and other mammals have been detected in apparently healthy bats. These include filoviruses, paramyxoviruses, and coronaviruses that cause severe diseases such as Ebola virus disease, Marburg haemorrhagic fever and severe acute respiratory syndrome (SARS) in humans. The evolution of flight in bats seem to have selected for a unique set of antiviral immune responses that control virus propagation, while limiting self-damaging inflammatory responses. Here, we summarize our current understanding of antiviral immune responses in bats and discuss their ability to co-exist with emerging viruses that cause serious disease in other mammals. We highlight how this knowledge may help us to predict viral spillovers into new hosts and discuss future directions for the field.

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Novel polyomaviruses in South American bats and their relationship to other members of the family Polyomaviridae

Cited by 49 publications

References 28 publications

Identification of an overprinting gene in Merkel cell polyomavirus provides evolutionary insight into the birth of viral genes

Identification of an overprinting gene in Merkel cell polyomavirus provides evolutionary insight into the birth of viral genes

No human virus sequences detected by next‐generation sequencing in benign verrucous skin tumors occurring in BRAF‐inhibitor‐treated patients

Novel Insights Into Immune Systems of Bats

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