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1.
Front Biosci (Landmark Ed) ; 26(10): 740-751, 2021 10 30.
Article in English | MEDLINE | ID: covidwho-1498507

ABSTRACT

Objectives: To quantify the integrated levels of ACE2 and TMPRSS2, the two well-recognized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry-related genes, and to further identify key factors contributing to SARS-CoV-2 susceptibility in head and neck squamous cell carcinoma (HNSC). Methods: We developed a metric of the potential for tissue infected with SARS-CoV-2 ("TPSI") based on ACE2 and TMPRSS2 transcript levels and compared TPSI levels between tumor and matched normal tissues across 11 tumor types. For further analysis of HNSC, weighted gene co-expression network analysis (WGCNA), functional analysis, and single sample gene set enrichment analysis (ssGSEA) were conducted to investigate TPSI-relevant biological processes and their relationship with the immune landscape. TPSI-related factors were identified from clinical and mutational domains, followed by lasso regression to determine their relative effects on TPSI levels. Results: TPSI levels in tumors were generally lower than in the normal tissues. In HNSC, the genes highly associated with TPSI were enriched in viral entry-related processes, and TPSI levels were positively correlated with both eosinophils and T helper 17 (Th17) cell infiltration. Furthermore, the site of onset, human papillomaviruses (HPV) status, and nuclear receptor binding SET domain protein 1 (NSD1) mutations were identified as the most important factors shaping TPSI levels. Conclusions: This study identified the infection risk of SARS-CoV-2 between tumor and normal tissues, and provided evidence for the risk stratification of HNSC.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/genetics , Carcinoma, Squamous Cell/genetics , Head and Neck Neoplasms/genetics , Serine Endopeptidases/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , COVID-19/virology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/virology , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/virology , Humans , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Serine Endopeptidases/metabolism , Virus Internalization
3.
J Med Virol ; 92(10): 2081-2086, 2020 10.
Article in English | MEDLINE | ID: covidwho-935097

ABSTRACT

SARS-CoV-2 is assumed to use angiotensin-converting enzyme 2 (ACE2) and other auxiliary proteins for cell entry. Recent studies have described conjunctival congestion in 0.8% of patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and there has been speculation that SARS-CoV-2 can be transmitted through the conjunctiva. However, it is currently unclear whether conjunctival epithelial cells express ACE2 and its cofactors. In this study, a total of 38 conjunctival samples from 38 patients, including 12 healthy conjunctivas, 12 melanomas, seven squamous cell carcinomas, and seven papilloma samples, were analyzed using high-throughput RNA sequencing to assess messenger RNA (mRNA) expression of the SARS-CoV-2 receptor ACE2 and its cofactors including TMPRSS2, ANPEP, DPP4, and ENPEP. ACE2 protein expression was assessed in eight healthy conjunctival samples using immunohistochemistry. Our results show that the SARS-CoV-2 receptor ACE2 is not substantially expressed in conjunctival samples on the mRNA (median: 0.0 transcripts per million [TPM], min: 0.0 TPM, max: 1.7 TPM) and protein levels. Similar results were obtained for the transcription of other auxiliary molecules. In conclusion, this study finds no evidence for a significant expression of ACE2 and its auxiliary mediators for cell entry in conjunctival samples, making conjunctival infection with SARS-CoV-2 via these mediators unlikely.


Subject(s)
COVID-19/virology , Carcinoma, Squamous Cell/virology , Eye Neoplasms/virology , Melanoma/virology , Papilloma/virology , Receptors, Virus/genetics , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/complications , COVID-19/pathology , COVID-19/surgery , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Case-Control Studies , Conjunctiva/pathology , Conjunctiva/surgery , Dipeptidyl Peptidase 4/genetics , Dipeptidyl Peptidase 4/metabolism , Eye Neoplasms/complications , Eye Neoplasms/pathology , Eye Neoplasms/surgery , Gene Expression , Glutamyl Aminopeptidase/genetics , Glutamyl Aminopeptidase/metabolism , Humans , Immunohistochemistry , Male , Melanoma/complications , Melanoma/pathology , Melanoma/surgery , Middle Aged , Papilloma/complications , Papilloma/pathology , Papilloma/surgery , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Virus/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism
4.
Vet Microbiol ; 240: 108491, 2020 Jan.
Article in English | MEDLINE | ID: covidwho-823740

ABSTRACT

Feline oral squamous cell carcinoma (FOSCC) may be the best naturally-occurring model of human head and neck squamous cell carcinoma (HNSCC). HNSCC can be broadly divided into human papillomavirus (HPV)-negative cancers and HPV-positive cancers where HPV is the causative agent. Previous studies in FOSCC have used both species-specific and species-nonspecific PCR primers that may be insensitive to the detection of PVs and other viruses that may be divergent from known sequences. ViroCap is a targeted capture and next generation sequencing tool that was designed to identify all known vertebrate DNA and RNA viruses. In this study we used a metagenomic approach using ViroCap for DNA viruses in 20 FOSCC, 9 normal feline oral mucosal, and 8 suspected PV positive control samples. We tested the hypothesis that viruses would be enriched in FOSCC compared to normal oral mucosa. The virome of the FOSCC and normal feline oral mucosa consisted of feline foamy virus in 7/20 and 2/9 (35% and 22%), feline torque teno virus in 2/20 and 0/9 (10% and 0%), alphaherpesvirus in 2/10 and 0/9 (10% and 0%), FIV (0% and 22%), Epstein-Barr virus in 1/20 and 0/9 (5% and 0%) and feline papillomavirus in 1/20 and 0/9 samples (5% and 0% respectively). Felis catus papillomavirus-3 was found in 1 of 20 FOSCC samples. A virus was not associated consistently with FOSCC. If PVs have a role in FOSCC it is at most a supplementary or uncommon role. FOSCC appears most closely related to HPV-negative HNSCC. Future research on FOSCC should focus on identifying genetic and environmental causes.


Subject(s)
Carcinoma, Squamous Cell/veterinary , Coinfection/veterinary , Mouth Neoplasms/veterinary , Papillomavirus Infections/veterinary , Viruses/classification , Animals , Carcinoma, Squamous Cell/virology , Cats , Coinfection/virology , DNA, Viral/genetics , Female , High-Throughput Nucleotide Sequencing , Male , Mouth Neoplasms/virology , Papillomavirus Infections/complications , Paraffin Embedding
5.
J Clin Pathol ; 73(11): 754-757, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-188172

ABSTRACT

In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pathologists can be exposed to infection handling surgical specimens. Guidelines related to safety procedures in the laboratory have been released. However, there is a lack of studies performed on biopsy and surgical resection specimens. Here we report the detection of SARS-CoV-2 in formalin-fixed paraffin-embedded samples from surgical resection of tongue squamous cell carcinoma of a patient who developed COVID-19 postsurgery. RNA of SARS-CoV-2 strain was detected in the tumour and the normal submandibular gland samples using real-time PCR-based assay. No viral RNA was found in metastatic and reactive lymph nodes. We demonstrated that SARS-CoV-2 RNA can be detected in routine histopathological samples even before COVID-19 disease development. These findings may give important information on the possible sites of infection or virus reservoir, and highlight the necessity of proper handling and fixation before sample processing.


Subject(s)
Betacoronavirus/isolation & purification , Carcinoma, Squamous Cell/surgery , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Postoperative Complications/diagnosis , Tissue Preservation/methods , Tongue Neoplasms/surgery , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Coronavirus Infections/etiology , Coronavirus Infections/virology , Fixatives , Formaldehyde , Humans , Male , Middle Aged , Pandemics , Paraffin Embedding , Pneumonia, Viral/etiology , Pneumonia, Viral/virology , Postoperative Complications/virology , RNA, Viral/analysis , RNA, Viral/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Tissue Fixation/methods , Tongue Neoplasms/complications , Tongue Neoplasms/pathology , Tongue Neoplasms/virology
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