There are many pieces of evidence, but one of the strongest is that when you take the mutations out of the ERV’s they become functional retroviruses.
Human Endogenous Retroviruses are expected to be the remnants of ancestral infections of primates by active retroviruses that have thereafter been transmitted in a Mendelian fashion.
Here, we derived in silico the sequence of the putative ancestral “progenitor” element of one of the most recently amplified family—the HERV-K family—and constructed it. This element, Phoenix, produces viral particles that disclose all of the structural and functional properties of a bona-fide retrovirus, can infect mammalian, including human, cells, and integrate with the exact signature of the presently found endogenous HERV-K progeny. We also show that this element amplifies via an extracellular pathway involving reinfection, at variance with the non-LTR-retrotransposons (LINEs, SINEs) or LTR-retrotransposons, thus recapitulating ex vivo the molecular events responsible for its dissemination in the host genomes. We also show that in vitro recombinations among present-day human HERV-K (also known as ERVK ) loci can similarly generate functional HERV-K elements, indicating that human cells still have the potential to produce infectious retroviruses.
The next big piece of evidence is that we can watch retroviruses produce new ERV’s right in front of us. Inserting into the host genome is a part of the life cycle for retroviruses.
The completion of the human genome sequence has made possible genome-wide studies of retroviral DNA integration. Here we report an analysis of 3,127 integration site sequences from human cells. We compared retroviral vectors derived from human immunodeficiency virus (HIV), avian sarcoma-leukosis virus (ASLV), and murine leukemia virus (MLV). Effects of gene activity on integration targeting were assessed by transcriptional profiling of infected cells. Integration by HIV vectors, analyzed in two primary cell types and several cell lines, strongly favored active genes. An analysis of the effects of tissue-specific transcription showed that it resulted in tissue-specific integration targeting by HIV, though the effect was quantitatively modest. Chromosomal regions rich in expressed genes were favored for HIV integration, but these regions were found to be interleaved with unfavorable regions at CpG islands. MLV vectors showed a strong bias in favor of integration near transcription start sites, as reported previously. ASLV vectors showed only a weak preference for active genes and no preference for transcription start regions. Thus, each of the three retroviruses studied showed unique integration site preferences, suggesting that virus-specific binding of integration complexes to chromatin features likely guides site selection.
Relationship between Integration Sites and Transcriptional Intensity in the Human Genome
The human chromosomes are shown numbered. HIV integration sites from all datasets in Table 1 are shown as blue “lollipops”; MLV integration sites are shown in lavender; and ASLV integration sites are shown in green. Transcriptional activity is shown by the red shading on each of the chromosomes (derived from quantification of nonnormalized EST libraries, see text). Centromeres, which are mostly unsequenced, are shown as grey rectangles.
That’s thousands of observed retroviral insertions into the human genome with their positions mapped.
A more esoteric piece of evidence is the long tandem repeats that are the bookends to the ERV sequence. When a retrovirus prepares a copy of the genome to be inserted into the host genome it creates two repeat regions at either end of the genome that are identical in sequence. That hallmark of viral insertion is seen in ERV’s.