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Viral Immunol. 2017 Nov;30(9):628-632. doi: 10.1089/vim.2017.0099. Epub 2017 Oct 13.

Hypothesis: RNA and DNA Viral Sequence Integration into the Mammalian Host Genome Supports Long-Term B Cell and T Cell Adaptive Immunity.

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1 Department of Infectious Diseases, St. Jude Children's Research Hospital , Memphis, Tennessee.
2 Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center , Memphis, Tennessee.
3 Max Planck Institute for Infection Biology , Berlin, Germany .
4 Humboldt University , Berlin, Germany .
5 The Laboratory for Molecular Infection Medicine Sweden (MIMS), Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University , Umeå, Sweden .
6 Trudeau Institute , Saranac Lake, New York.


Viral sequence integration into the mammalian genome has long been perceived as a health risk. In some cases, integration translates to chronic viral infection, and in other instances, oncogenic gene mutations occur. However, research also shows that animal cells can benefit from integrated viral sequences (e.g., to support host cell development or to silence foreign invaders). Here we propose that, comparable with the clustered regularly interspaced short palindromic repeats that provide bacteria with adaptive immunity against invasive bacteriophages, animal cells may co-opt integrated viral sequences to support immune memory. We hypothesize that host cells express viral peptides from open reading frames in integrated sequences to boost adaptive B cell and T cell responses long after replicating viruses are cleared. In support of this hypothesis, we examine previous literature describing (1) viruses that infect acutely (e.g., vaccinia viruses and orthomyxoviruses) followed by unexplained, long-term persistence of viral nucleotide sequences, viral peptides, and virus-specific adaptive immunity, (2) the high frequency of endogenous viral genetic elements found in animal genomes, and (3) mechanisms with which animal host machinery supports foreign sequence integration.


CRISPR; hypothesis; viral sequence integration

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