used for any HERV insertions. Cross-sectional dating has been used to suggest that two members of HERV-K (HML2), HERV-K106 and HERV-K116, were active in the last 800,000 years and that HERV-K106 may have infected modern humans 150,000 years ago. However, the absence of known infectious members of the HERV-K (HML2) family, and the lack of elements with a full coding potential within the published human genome sequence, suggests to some that the family is less likely to be active at present. In 2006 and 2007, researchers working independently in France and the US recreated functional versions of HERV-K (HML2). Expression of HERV proteins The expression of HERV-K, a biologically active family of HERV, produces proteins found in placenta. Furthermore, the expression of the envelope genes of HERV-W (ERVW-1) and HERV-FRD (ERVFRD-1) produces syncytins which are important for the generation of the syncytiotrophoblast cell layer during placentogenesis by inducing cell-cell fusion. The HUGO Gene Nomenclature Committee (HGNC) approves gene symbols for transcribed human ERVs. Functional impact MER41.AIM2 is an HERV that regulates the transcription of AIM2 (Absent in Melanoma 2) which encodes for a sensor of foreign cytosolic DNA. This acts as a binding site for AIM2, meaning that it is necessary for the transcription of AIM2. Researchers had shown this by deleting MER41.AIM2 in HeLa cells using CRISPR/Cas9, leading to an undetectable transcript level of AIM2 in modified HeLa cells. The control cells, which still contained the MER41.AIM2 ERV, were observed with normal amounts of AIM2 transcript. In terms of immunity, researchers concluded that MER41.AIM2 is necessary for an inflammatory response to infection. Activation by exogenous viruses Considerable evidence indicate that HERVs can be reactivated by viral infections, such as: 1) retroviruses – human immunodeficiency virus type-1 (HIV-1), human T-lymphotropic virus 1 (HTLV-1); 2) RNA viruses – influenza A virus, hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus-2 (SARSCoV-2); 3) DNA viruses – herpes simplex virus type-1 (HSV-1), Epstein-Barr virus (EBV), human cytomegalovirus (CMV), Kaposi’s sarcoma-associated herpesvirus (KSHV) Several studies have shown that EBV is able to transactivate the expression of the normally inactive HERV-K18 Env protein, e.g., interacting with resting B cells via CD21 receptor. Further studies revealed that the mechanism of transactivation depends on the expression of the major EBV late gene transactivator, EBNA-2. In-depth analysis completed the picture identifying the EBV latent membrane protein LMP-2A as a strong candidate for the HERV-K18 transactivation. HERV-K18 has also