An endogenous retrovirus presumed to have been endogenized or relocated recently in a marsupial, the red-necked wallaby

An albino infant wallaby was born to a mother with the wild-type body color. PCR and sequencing analyses of <i>TYR</i> (encoding tyrosinase, which is essential for melanin biosynthesis) of this albino wallaby revealed a 7.1-kb-long DNA fragment inserted in the first exon. Because the fragment carried long terminal repeats, we assumed it to be a copy of an endogenous retrovirus, which we named <i>walb</i>. We cloned other <i>walb</i> copies residing in the genomes of this species and another wallaby species. The copies exhibited length variation, and the longest copy (>8.0 kb) contained open reading frames whose deduced amino acid sequences were well aligned with those of <i>gag</i>, <i>pol</i>, and <i>env</i> of retroviruses. It is not known through which of the following likely processes the walb copy was inserted into <i>TYR</i>: endogenization (infection of a germline cell by an exogenous virus), reinfection (infection by a virus produced from a previously endogenized provirus), or retrotransposition (intracellular relocation of a provirus). In any case, the insertion into <i>TYR</i> is considered to have been a recent event on an evolutionary timescale because albino mutant alleles generally do not persist for long because of their deleterious effects in wild circumstances.

Analysis of Simian Endogenous Retrovirus (SERV) Full-Length Proviruses in Old World Monkey Genomes

Simian endogenous retrovirus, SERV, is a successful germ line invader restricted to Old World monkey (OWM) species. (1) Background: The availability of high-quality primate genomes warrants a study of the characteristics, evolution, and distribution of SERV proviruses. (2) Methods: Cercopithecinae OWM genomes from public databases were queried for the presence of full-length SERV proviruses. A dataset of 81 Cer-SERV genomes was generated and analyzed. (3) Results: Full-length Cer-SERV proviruses were mainly found in terrestrial OWM, and less so in arboreal, forest- dwelling monkeys. Phylogenetic analysis confirmed the existence of two genotypes, Cer-SERV-1 and Cer-SERV-2, with Cer-SERV-1 showing evidence of recent germ-line expansions. Long Terminal Repeat (LTR) variation indicated that most proviruses were of a similar age and were estimated to be between <0.3 and 10 million years old. Integrations shared between species were relatively rare. Sequence analysis further showed extensive CpG methylation-associated mutations, variable Primer Binding Site (PBS) use with Cer-SERV-1 using PBSlys3 and Cer-SERV-2 using PBSlys1,2, and the recent gain of LTR motifs for transcription factors active during embryogenesis in Cer-SERV-1. (4) Conclusions: sequence analysis of 81 SERV proviruses from Cercopithecinae OWM genomes provides evidence for the adaptation of this retrovirus to germ line reproduction.

ICTV Virus Taxonomy Profile: Retroviridae 2021

Viruses in the family Retroviridae are found in a wide variety of vertebrate hosts. Enveloped virions are 80–100 nm in diameter with an inner core containing the viral genome and replicative enzymes. Core morphology is often characteristic for viruses within the same genus. Replication involves reverse transcription and integration into host cell DNA, resulting in a provirus. Integration into germline cells can result in a heritable provirus known as an endogenous retrovirus. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Retroviridae, which is available at ictv.global/report/retroviridae.

Endogenous Retrovirus-Derived lnc-ALVE1-AS1 Exerts Antiviral Defense Against ALV-J Infection in Chicken Macrophages

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections dating back many millions of years, and their derived transcripts with viral signatures are important sources of long noncoding RNAs (lncRNAs). We have previously shown that the chicken ERV-derived lncRNA lnc-ALVE1-AS1 exerts antiviral innate immunity in chicken embryo fibroblasts. However, it is not clear whether this endogenous retroviral RNA has a similar function in immune cells. Here, we found that lnc-ALVE1-AS1 was persistently inhibited in chicken macrophages after avian leukosis virus subgroup J (ALV-J) infection. Furthermore, overexpression of lnc-ALVE1-AS1 significantly inhibited the proliferation of exogenous ALV-J, whereas knockdown of lnc-ALVE1-AS1 promoted the proliferation of ALV-J in chicken macrophages. This phenomenon is attributed to the induction of antiviral innate immunity by lnc-ALVE1-AS1 in macrophages, whereas knockdown of lnc-ALVE1-AS1 had the opposite effect. Mechanistically, lnc-ALVE1-AS1 can be sensed by the cytosolic pattern recognition receptor TLR3 and trigger the type I interferons response. The present study provides novel insights into the antiviral defense of ERV-derived lncRNAs in macrophages and offers new strategies for future antiviral solutions.

Vaccination against the Koala Retrovirus (KoRV): Problems and Strategies

The koala retrovirus (KoRV) is spreading in the koala population from the north to the south of Australia and is also in the process of endogenization into the koala genome. Virus infection is associated with tumorigenesis and immunodeficiency and is contributing to the decline of the animal population. Antibody production is an excellent marker of retrovirus infection; however, animals carrying endogenous KoRV are tolerant. Therefore, the therapeutic immunization of animals carrying endogenous KoRV seems to be ineffective. Using the recombinant transmembrane (TM) envelope protein of the KoRV, we immunized goats, rats and mice, obtaining in all cases neutralizing antibodies which recognize epitopes in the fusion peptide proximal region (FPPR), and in the membrane-proximal external region (MPER). Immunizing several animal species with the corresponding TM envelope protein of the closely related porcine endogenous retrovirus (PERV), as well as the feline leukemia virus (FeLV), we also induced neutralizing antibodies with similar epitopes. Immunizing with the TM envelope protein in addition to the surface envelope proteins of all three viruses resulted in higher titers of neutralizing antibodies. Immunizing KoRV-negative koalas with our vaccine (which is composed of both envelope proteins) may protect these animals from infection, and these may be the starting points of a virus-free population.

Neuron-specific chromosomal megadomain organization is adaptive to recent retrotransposon expansions

Regulatory mechanisms associated with repeat-rich sequences and chromosomal conformations in mature neurons remain unexplored. Here, we map cell-type specific chromatin domain organization in adult mouse cerebral cortex and report strong enrichment of Endogenous Retrovirus 2 (ERV2) repeat sequences in the neuron-specific heterochromatic B2NeuN+ megabase-scaling subcompartment. Single molecule long-read sequencing and comparative Hi-C chromosomal contact mapping in wild-derived SPRET/EiJ (Mus spretus) and laboratory inbred C57BL/6J (Mus musculus) reveal neuronal reconfigurations tracking recent ERV2 expansions in the murine germline, with significantly higher B2NeuN+ contact frequencies at sites with ongoing insertions in Mus musculus. Neuronal ablation of the retrotransposon silencer Kmt1e/Setdb1 triggers B2NeuN+ disintegration and rewiring with open chromatin domains enriched for cellular stress response genes, along with severe neuroinflammation and proviral assembly with infiltration of dendrites . We conclude that neuronal megabase-scale chromosomal architectures include an evolutionarily adaptive heterochromatic organization which, upon perturbation, results in transcriptional dysregulation and unleashes ERV2 proviruses with strong neuronal tropism.