Comprehensive Characterization of the Human Endogenous Retrovirus HERV-K(HML-6) Group: Overview of Structure, Phylogeny, and Contribution to the Human Genome

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Animal retroviruses are known for their transforming potential, and this is also true for the ones hosted by humans, which have gathered expanding attention as one of the potent causative agents in various disease, including specific cancer types. For instance, Human T Lymphotropic virus (HTLV) is a well-studied class of oncoviruses causing T cell leukemia, while human immunodeficiency virus (HIV) leads to acquired immunodeficiency syndrome (AIDS), which is linked to a series of defining cancers including Kaposi sarcoma, certain types of non-Hodgkin lymphoma, and cervical cancer. Of note, in addition to these “modern” exogenous retroviruses, our genome harbors a staggering number of human endogenous retroviruses (HERVs). HERVs are the genetic remnants of ancient retroviral germline infection of human ancestors and are typically silenced in normal tissues due to inactivating mutations and sequence loss. While some HERV elements have been appropriated and contribute to human physiological functions, others can be reactivated through epigenetic dysregulations to express retroviral elements and promote carcinogenesis. Conversely, HERV replication intermediates or protein products can also serve as intrinsic pathogen-associated molecular patterns that cause the immune system to interpret it as an exogenous infection, thereby stimulating immune responses against tumors. As such, HERVs have also been targeted as a potential internal strategy to sensitize tumor cells for promising immunotherapies. In this review, we discuss the dynamic role of human retroviruses in cancer development, focusing on HIV and HERVs contribution. We also describe potential treatment strategies, including immunotherapeutic targeting of HERVs, inhibiting DNA methylation to expose HERV signatures, and the use of antiretroviral drugs against HIV and HERVs, which can be employed as prospective anti-cancer modalities.

Section: Herv Contribution To Cancer At the Protein Levelmentioning

confidence: 71%

Contribution of Human Retroviruses to Disease Development—A Focus on the HIV– and HERV–Cancer Relationships and Treatment Strategies

Grandi

Palanivelu

Lin

2020

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“…In addition, the HERV-K group (HML1-HML10) can also be classified into type I and II proviruses, however phylogenetic type I and II classification from the HERV-K group is not the same for all HML subtypes. For instance, HERV-K HML-2, HML-6 and HLM-10 subtypes are classified into type I or II, based on differences from their genomes; however type I and II from each of them are unrelated [ 21 , 22 , 23 , 24 ]. Moreover, phylogenetic analysis using LTR sequences can be used to classify HERV-K, HML-2 subtype, into three subgroups, known as LTR5Hs, LTR5A and LTR5B [ 2 , 19 , 24 , 25 ].…”

Section: Hervs: Classification and Genomementioning

confidence: 99%

Human Endogenous Retrovirus K in Cancer: A Potential Biomarker and Immunotherapeutic Target

Curty

Marston

Rougvie

et al. 2020

In diseases where epigenetic mechanisms are changed, such as cancer, many genes show altered gene expression and inhibited genes become activated. Human endogenous retrovirus type K (HERV-K) expression is usually inhibited in normal cells from healthy adults. In tumor cells, however, HERV-K mRNA expression has been frequently documented to increase. Importantly, HERV-K-derived proteins can act as tumor-specific antigens, a class of neoantigens, and induce immune responses in different types of cancer. In this review, we describe the function of the HERV-K HML-2 subtype in carcinogenesis as biomarkers, and their potential as targets for cancer immunotherapy.

“…The HERV coordinates provided in these databases are, hence, the most accurate and well-annotated. Example of HERV groups deeply studied are the HERV-W, and several HML subgroups [ 6 , 32 , 47 , 48 , 49 , 50 ].…”

Section: Identification Of Hervs In the Human Genomementioning

confidence: 99%

High-Throughput Sequencing is a Crucial Tool to Investigate the Contribution of Human Endogenous Retroviruses (HERVs) to Human Biology and Development

Pisano

Grandi

Tramontano

2020

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Human Endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that represent a large fraction of our genome. Their transcriptional activity is finely regulated in early developmental stages and their expression is modulated in different cell types and tissues. Such activity has an impact on human physiology and pathology that is only partially understood up to date. Novel high-throughput sequencing tools have recently allowed for a great advancement in elucidating the various HERV expression patterns in different tissues as well as the mechanisms controlling their transcription, and overall, have helped in gaining better insights in an all-inclusive understanding of the impact of HERVs in biology of the host.