Hosseiniporgham Sepideh, Sechi Leonardo Antonio
Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy.
Unit of Microbiology and Virology, Agency of University Hospital (AOU), 07100 Sassari, Italy.
Vaccines (Basel). 2023 Mar 28;11(4):751. doi: 10.3390/vaccines11040751.
The footprint of human endogenous retroviruses (HERV), specifically HERV-K, has been found in malignancies, such as melanoma, teratocarcinoma, osteosarcoma, breast cancer, lymphoma, and ovary and prostate cancers. HERV-K is characterized as the most biologically active HERV due to possession of open reading frames (ORF) for all Gag, Pol, and Env genes, which enables it to be more infective and obstructive towards specific cell lines and other exogenous viruses, respectively. Some factors might contribute to carcinogenicity and at least one of them has been recognized in various tumors, including overexpression/methylation of long interspersed nuclear element 1 (LINE-1), HERV-K Gag, and Env genes themselves plus their transcripts and protein products, and HERV-K reverse transcriptase (RT). Therapies effective for HERV-K-associated tumors mostly target invasive autoimmune responses or growth of tumors through suppression of HERV-K Gag or Env protein and RT. To design new therapeutic options, more studies are needed to better understand whether HERV-K and its products (Gag/Env transcripts and HERV-K proteins/RT) are the initiators of tumor formation or just the disorder's developers. Accordingly, this review aims to present evidence that highlights the association between HERV-K and tumorigenicity and introduces some of the available or potential therapies against HERV-K-induced tumors.
人类内源性逆转录病毒（HERV）的踪迹，特别是HERV-K，已在恶性肿瘤中被发现，如黑色素瘤、畸胎癌、骨肉瘤、乳腺癌、淋巴瘤以及卵巢癌和前列腺癌。HERV-K被认为是生物学活性最强的HERV，因为它拥有所有Gag、Pol和Env基因的开放阅读框（ORF），这使其分别对特定细胞系更具感染性，并对其他外源病毒更具阻碍作用。一些因素可能导致致癌性，并且至少其中之一已在各种肿瘤中得到确认，包括长散在核元件1（LINE-1）、HERV-K Gag和Env基因本身及其转录本和蛋白质产物，以及HERV-K逆转录酶（RT）的过表达/甲基化。对HERV-K相关肿瘤有效的治疗方法大多通过抑制HERV-K Gag或Env蛋白以及RT来靶向侵袭性自身免疫反应或肿瘤生长。为了设计新的治疗方案，需要更多研究来更好地了解HERV-K及其产物（Gag/Env转录本和HERV-K蛋白/RT）是肿瘤形成的引发因素还是仅仅是该病症的发展因素。因此，本综述旨在呈现突出HERV-K与致瘤性之间关联的证据，并介绍一些针对HERV-K诱导肿瘤的现有或潜在治疗方法。
