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Whole-Transcriptome Sequencing–Based Profiling of the Cutaneous Virome in Patients With Secondary Immunodeficiency Publisher



Youssefian L1, 2 ; Saeidian AH2, 3 ; Saffarian Z4, 5 ; Ariamanesh M6 ; Abdollahimajd F7 ; Molkara S8 ; Shahididadras M7 ; Diab R7 ; Vahidnezhad F9 ; Zeinali S10 ; Beziat V11, 12, 13 ; Jouanguy E11, 12, 13 ; Casanova JL11, 12, 13, 14, 15 ; Uitto J16 Show All Authors
Authors
  1. Youssefian L1, 2
  2. Saeidian AH2, 3
  3. Saffarian Z4, 5
  4. Ariamanesh M6
  5. Abdollahimajd F7
  6. Molkara S8
  7. Shahididadras M7
  8. Diab R7
  9. Vahidnezhad F9
  10. Zeinali S10
  11. Beziat V11, 12, 13
  12. Jouanguy E11, 12, 13
  13. Casanova JL11, 12, 13, 14, 15
  14. Uitto J16
  15. Vahidnezhad H2, 17, 18, 19
Show Affiliations
Authors Affiliations
  1. 1. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United States
  2. 2. Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, United States
  3. 3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States
  4. 4. Imam Khomeini Hospital, Tehran University of Medical Science, Tehran, Iran
  5. 5. Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
  7. 7. Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  8. 8. Department of Dermatology, Gonabad University of Medical Sciences, Gonabad, Iran
  9. 9. UCSC Silicon Valley Extension, University of California, Santa Cruz, CA, United States
  10. 10. Kawsar Human Genetics Research Center, Tehran, Iran
  11. 11. St Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, United States
  12. 12. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, Necker Hospital for Sick Children, Paris, U1163, France
  13. 13. Imagine Institute, Paris University, Paris, France
  14. 14. Howard Hughes Medical Institute, New York, NY, United States
  15. 15. Department of Pediatrics, Necker Hospital for Sick Children, Paris, France
  16. 16. Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States
  17. 17. Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, United States
  18. 18. Department of Pediatrics, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, United States
  19. 19. Department of Dermatology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, United States

Source: JID Innovations Published:2024


Abstract

Most viral infections can be self-limited, with no requirement for medical intervention. However, the same viruses can cause severe diseases in patients with compromised immunity due to single-gene diseases, acquired immune deficiency syndrome, or hematologic malignancies or those receiving immunosuppressive drugs. Occasionally, these immunocompromised patients harbor >1 infectious agent, requiring several concomitant diagnostic tests. We have developed, to our knowledge, a previously unreported whole-transcriptome sequencing–based pipeline that allows virome profiling, quantitation, and expression pattern analysis of 926 distinct viruses by sequencing of RNA isolated from a single lesional skin biopsy. This pipeline can also explore host genetics if there is a Mendelian predisposition to infection. We applied this pipeline to 6 Iranian patients with viral-induced skin lesions associated with immune deficiency secondary to HIV, human T-lymphotropic virus 1, chronic lymphocytic leukemia, and post transplant immunosuppression. In 5 cases, definitive human papillomavirus infections were identified, some caused by multiple viral types. In addition to human papillomavirus, coinfection with other viruses (Merkle cell polyomavirus, cytomegalovirus, and human herpesvirus 4) was detected in some lesions. In 1 case, whole-transcriptome sequencing validated the clinical diagnosis of adult T-cell leukemia/lymphoma in a patient with an initial diagnosis of mycosis fungoides/Sezary syndrome. These findings attest to the power of whole-transcriptome sequencing in profiling the cutaneous virome in the context of compromised immunity. © 2024 The Authors
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