Analysis of Class I Major Histocompatibility Complex Gene Transcription in Human Tumors Caused by Human Papillomavirus Infection

Gameiro, Steven F.; Zhang, Ali; Ghasemi, Farhad; Barrett, John W.; Nichols, Anthony C.; Mymryk, Joe S.

doi:10.3390/v9090252

Submit to this Journal Review for this Journal Edit a Special Issue

Article Menu

...

Open AccessArticle

Analysis of Class I Major Histocompatibility Complex Gene Transcription in Human Tumors Caused by Human Papillomavirus Infection

¹,

²,

²,

^2,3,4

and

Joe S. Mymryk

^1,2,3,4,*

Department of Microbiology and Immunology, The University of Western Ontario, London, ON N6A 3K7, Canada

Department of Otolaryngology, Head & Neck Surgery, The University of Western Ontario, London, ON N6A 3K7, Canada

Department of Oncology, The University of Western Ontario, London, ON N6A 3K7, Canada

⁴

London Regional Cancer Program, Lawson Health Research Institute, London, ON N6C 2R5, Canada

Author to whom correspondence should be addressed.

Academic Editor: Eric O. Freed

Viruses 2017, 9(9), 252; https://doi.org/10.3390/v9090252

Received: 12 July 2017 / Revised: 31 August 2017 / Accepted: 2 September 2017 / Published: 10 September 2017

(This article belongs to the Special Issue Viral Subversion of Transcriptional Control)

View Full-Text Download PDF

Browse Figures

Citation Export

Abstract

Oncoproteins from high-risk human papillomaviruses (HPV) downregulate the transcription of the class I major histocompatibility complex (MHC-I) antigen presentation apparatus in tissue culture model systems. This could allow infected or transformed cells to evade the adaptive immune response. Using data from over 800 human cervical and head & neck tumors from The Cancer Genome Atlas (TCGA), we determined the impact of HPV status on the mRNA expression of all six MHC-I heavy chain genes, and the β2 microglobulin light chain. Unexpectedly, these genes were all expressed at high levels in HPV positive (HPV+) cancers compared with normal control tissues. Indeed, many of these genes were expressed at significantly enhanced levels in HPV+ tumors. Similarly, the transcript levels of several other components of the MHC-I peptide-loading complex were also high in HPV+ cancers. The coordinated expression of high mRNA levels of the MHC-I antigen presentation apparatus could be a consequence of the higher intratumoral levels of interferon γ in HPV+ carcinomas, which correlate with signatures of increased infiltration by T- and NK-cells. These data, which were obtained from both cervical and oral tumors in large human cohorts, indicates that HPV oncoproteins do not efficiently suppress the transcription of the antigen presentation apparatus in human tumors. View Full-Text

Keywords: human papillomavirus; MHC-I; major histocompatibility complex; antigen presentation; immune evasion; head & neck carcinoma; cervical carcinoma

▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share and Cite

MDPI and ACS Style

Gameiro, S.F.; Zhang, A.; Ghasemi, F.; Barrett, J.W.; Nichols, A.C.; Mymryk, J.S. Analysis of Class I Major Histocompatibility Complex Gene Transcription in Human Tumors Caused by Human Papillomavirus Infection. Viruses 2017, 9, 252. https://doi.org/10.3390/v9090252

AMA Style

Gameiro SF, Zhang A, Ghasemi F, Barrett JW, Nichols AC, Mymryk JS. Analysis of Class I Major Histocompatibility Complex Gene Transcription in Human Tumors Caused by Human Papillomavirus Infection. Viruses. 2017; 9(9):252. https://doi.org/10.3390/v9090252

Chicago/Turabian Style

Gameiro, Steven F., Ali Zhang, Farhad Ghasemi, John W. Barrett, Anthony C. Nichols, and Joe S. Mymryk. 2017. "Analysis of Class I Major Histocompatibility Complex Gene Transcription in Human Tumors Caused by Human Papillomavirus Infection" Viruses 9, no. 9: 252. https://doi.org/10.3390/v9090252

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

Analysis of Class I Major Histocompatibility Complex Gene Transcription in Human Tumors Caused by Human Papillomavirus Infection

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI