Novel Gammapapillomavirus type in the nasal cavity of a wild red colobus (Piliocolobus tephrosceles)
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Papillomaviruses (PVs) are double-stranded, circular, epitheliotropic DNA viruses causing benign warts (papillomas) or inducing dysplasia that can progress to cancer. Although they have been identified in all vertebrate taxa, most classified types are human PVs (HPVs); relatively little is known about PVs in other species. Here we characterize a novel Gammapapillomavirus type, PtepPV1, from a nasal swab of a wild red colobus ( Piliocolobus tephrosceles ) in Kibale National Park, Uganda. The virus has a genome of 6576 bases, encoding the seven canonical early (E) ORFs (E6, E7, E1, E2, E4, E1^E4 and E8^E2) and two late (L) ORFs (L1 and L2) of the gammapapillomaviruses, and is 81.0% similar to HPV-mSK_118, detected in a cutaneous wart from an immunocompromised human patient, in the L1 gene at the amino acid level. Alphapapillomaviruses (genus Alphapapillomavirus ) cause anogenital carcinomas such as cervical cancer and have been described previously in several nonhuman primates. However, the first gammapapillomavirus (genus Gammapapillomavirus ), which cause transient cutaneous infections, was not described until 2019 in a healthy rhesus macaque ( Macaca mulatta ) genital swab. The new virus from red colobus, PtepPV1, has many genomic features encoded by high-risk oncogenic PVs, such as the E7 gene LXSXE and CXXC motifs, suggesting potential for pRb and zinc-finger binding, respectively. To our knowledge, PtepPV1 is also the first reported nonhuman primate PV found in the nasal cavity. PtepPV1 expands the known host range, geographical distribution, tissue tropism and biological characteristics of nonhuman primate PVs.
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I am pleased to tell you that your article has now been accepted for publication in Access Microbiology. The work presented is clear and the arguments well formed. The manuscript is well written and contributes to the literature. Thank you for addressing all reviewers comments satisfactorily and in a timely manner.
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Thank you for submitting your manuscript for publication in Access Microbiology. It has been examined by expert reviewers who have concluded that the work is well written and of interest to the readership of Access Microbiology. However, based on the comments received, a minor amendment of this manuscript will be required. I will be pleased to consider a revised manuscript along with a document including a point by point response to each of the reviewers comments. Your revised manuscript may be returned to one or more of the original reviewers, along with your itemised response to the reviewers’ comments.
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Comments to Author
In this study, the authors report the identification and genomic characterization of a novel papillomavirus type from a red colobus (Piliocolobus tephrosceles) - PtepPV1, the first described gammapapillomavirus infecting a colobus and the first nonhuman primate papillomavirus found in the nasal cavity. Phylogenetic analysis showed that PtepPV1 is most closely related to the human papillomavirus HPV-mSK_118. Therefore, the identification and characterization of PtepPV1 improves our knowledge of the molecular diversity, tissue tropism, and evolutionary history of primate papillomaviruses. I found the manuscript overall to be well written and concise. The table and figures are clear and the data are discussed appropriately. Since the results presented in the study also represent the genomic …
Comments to Author
In this study, the authors report the identification and genomic characterization of a novel papillomavirus type from a red colobus (Piliocolobus tephrosceles) - PtepPV1, the first described gammapapillomavirus infecting a colobus and the first nonhuman primate papillomavirus found in the nasal cavity. Phylogenetic analysis showed that PtepPV1 is most closely related to the human papillomavirus HPV-mSK_118. Therefore, the identification and characterization of PtepPV1 improves our knowledge of the molecular diversity, tissue tropism, and evolutionary history of primate papillomaviruses. I found the manuscript overall to be well written and concise. The table and figures are clear and the data are discussed appropriately. Since the results presented in the study also represent the genomic characterization of PtepPV1, the authors should describe the methodological approach used to determine the open reading frames (ORFs) and putative functional motifs/domains. Furthermore, it is not clear whether there is experimental evidence confirming the presence and function of the molecular features of the virus. If the results are based only on in silico molecular analyses, this should be acknowledged in the "Materials and Methods" and "Discussion" sections. In the "Results" section, it is reported that the PtepPV1 genome consists of nine ORFs encoding viral proteins and a non-coding regulatory region URR. The authors mention the identification of several putative functional motifs/domains in the URR, other genomic regions, and the E7 viral protein. The positions of all mentioned functional motifs/domains in the nucleotide/amino acid sequences should be reported in the manuscript, as this could be important information for the genomic characterization of newly discovered gammapapillomaviruses in the future. Previous similar studies have also described consensus sequences of different functional motifs/domains in other papillomavirus proteins that are important for the progression of the viral life cycle (e.g., PDZ-binding motif in the E6 oncoprotein). It is not entirely clear from the manuscript whether the amino acid sequences of other PtepPV1 proteins were not analysed or whether the putative functional motifs/domains were not present there. In the "Materials and Methods" section, it is mentioned that the pairwise similarities between the complete nucleotide/amino acid sequences of individual genes/proteins were calculated. Therefore, the nucleotide sequence identity data should also be listed in the table in the "Results" section. Minor comments: - The paragraph describing the "PV diagnostic PCR" should include information about the expected size of the PCR products and the length of the PtepPV1 genome sequenced with the ABI 3130xl Genetic Analyzer. - Line 200: Cpen1 and Cpen2 should be corrected to CpenPV1 and CpenPV2. - Line 210 states that the amino acid sequence identity of PtepPV1 and HPV-mSK_118 L1 ORFs is 83.3%, but in Table 1 it is given as 81%.
Please rate the manuscript for methodological rigour
Good
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
Dear authors, It was a pleasure to review your manuscript. The article you have presented demonstrates a well-structured and meticulously executed study. The research objectives are clearly defined and effectively achieved, showcasing a solid grasp of the subject matter. The comprehensive literature review forms a robust foundation for your research. Your methods are meticulously detailed, enabling experiment replication and effectively addressing the research questions with relevant controls. I commend you for adhering to relevant ethical guidelines throughout your study, including adherence to the Weatherall Report's guidelines on the use of non-human primates in research, and obtaining approvals from the Uganda Wildlife Authority, the Uganda National Council for Science and Technology, and the …
Comments to Author
Dear authors, It was a pleasure to review your manuscript. The article you have presented demonstrates a well-structured and meticulously executed study. The research objectives are clearly defined and effectively achieved, showcasing a solid grasp of the subject matter. The comprehensive literature review forms a robust foundation for your research. Your methods are meticulously detailed, enabling experiment replication and effectively addressing the research questions with relevant controls. I commend you for adhering to relevant ethical guidelines throughout your study, including adherence to the Weatherall Report's guidelines on the use of non-human primates in research, and obtaining approvals from the Uganda Wildlife Authority, the Uganda National Council for Science and Technology, and the University of Wisconsin Animal Care and Use Committee prior to study initiation. Your results are significant and well-presented, making a substantial contribution to our understanding of papillomaviruses, particularly in terms of their diversity and tropism. The interpretation of results is robust, grounded in solid data and supported by appropriate references to existing literature. You have effectively contextualized your findings within broader scientific frameworks, underscoring the relevance of your work. However, I advise caution in assigning tropism for this gammapapillomavirus and suggest discussing the possibility of opportunistic tropism. Given the absence of lesions in the tissue and the sensitivity of molecular detection techniques, it may indicate that the virus is not actively infecting nasal tissue but rather present due to contamination from oral mucosa vía saliva or from the skin during the grooming. Overall, your article is well-written and concise, maintaining an appropriate length without sacrificing detail. The tables and figures are effectively used to support the text. This manuscript represents a significant and well-executed contribution to the field, reflecting rigorous research and thoughtful analysis.
Please rate the manuscript for methodological rigour
Very good
Please rate the quality of the presentation and structure of the manuscript
Very good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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