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Review
. 2024 Sep 27:14:1439292.
doi: 10.3389/fcimb.2024.1439292. eCollection 2024.

Human endogenous retroviruses and exogenous viral infections

Chenxuan Bao  1 , Qing Gao  1 , Huayuan Xiang  1 , Yuxuan Shen  2 , Qiaoqiao Chen  1 , Qianqian Gao  1 , Yuanfei Cao  1 , Mengyu Zhang  1 , Wenyuan He  1 , Lingxiang Mao  1
Affiliations
Review

Human endogenous retroviruses and exogenous viral infections

Chenxuan Bao et al. Front Cell Infect Microbiol. .

Abstract

The human genome harbors many endogenous retroviral elements, known as human endogenous retroviruses (HERVs), which have been integrated into the genome during evolution due to infections by exogenous retroviruses. Accounting for up to 8% of the human genome, HERVs are tightly regulated by the host and are implicated in various physiological and pathological processes. Aberrant expression of HERVs has been observed in numerous studies on exogenous viral infections. In this review, we focus on elucidating the potential roles of HERVs during various exogenous viral infections and further discuss their implications in antiviral immunity.

Keywords: HERV-K; HERV-W; active immunity; antiviral immunity; human endogenous retroviruses (HERVs); virus infection.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Proviral genomic structure and transcripts of HERV-K. The precursor sequence of HERV-K includes two flanking long-terminal repeats (LTRs) and four open reading frames (ORFs), and the sequences of four ORFs are overlapped (shown by colored lines). The two LTRs consist of U3 and U5 regions separated by an R fragment. The full-length HERV-K precursor sequence produces four transcripts. Transcript 1 contains three ORFs encoding Gag, Pro, and Pol, all sharing a common start codon. These ORFs overlap in their DNA sequences but not in their amino acid sequences, and they are translated via ribosomal frameshifting. The translation products are subsequently processed to generate the final functional subunits, including matrix (MA), capsid (CA), and nucleocapsid (NC) from Gag; dUTPase from the Gag-Pro junction; and reverse transcriptase (RT), RNase H, and integrase (IN) from Pol. Transcript 2 encodes Env, which is composed of the signal peptide (SP), surface (SU), and transmembrane (TM) subunits. Transcript 3 is produced from type 1, which has a 292-bp deletion at the pol–env junction. This deletion eliminates the original splice donor (SD) site, leading to the utilization of an upstream SD site (SD-NP9), and the transcript encodes NP9. Transcript 4 is produced from type 2, which has no nucleotide deletion and encodes the Rec.
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