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ERV

A whale of a virus story

15 July 2021 by Vincent Racaniello

The ancestors of cetaceans (whales, dolphins, and porpoises) moved from land to the sea over 50 million years ago. Many viruses infect cetaceans, but how they evolved during the shift from land to sea is unknown. Fossilized retroviral genomes integrated into cetacean DNA provide insight into this question.

The retroviral reproduction cycle involves the conversion of viral RNA into DNA followed by integration in host chromosomes, leading to what is know as proviral DNA. If this integration event occurs in germ cells, the provirus may be transmitted to offspring for many generations. Analysis of cetacean endogenous retroviral DNA (ERV) provides insight into when in evolution these viruses were acquired.

Cetacean retroviruses may have arisen in two ways. In the land-to-water scenario (pictured), the terrestrial ancestor of cetaceans was infected, and then carried the retrovirus into the oceans. In the secondary host switching scenario, only after cetaceans were in the oceans were they infected by cross-species transmission from other non-cetacean mammals.

Analysis of cetacean ERVs provides support for both scenarios. A search of the sequenced genomes of mysticetes (baleen whales) and odontocetes (toothed whales) revealed 8,724 ERVs. Phylogenetic analysis of these ERVs places them into 315 distinct lineages. Of these, 298 are found in both mysticetes and odontocetes, implying that they were present before these lineages diverged. The copy numbers of these ERVs are very low, suggesting that they did not proliferate after their hosts entered the waters. Some are related to ERVs found in hippopotamuses, which share a common ancestor with cetaceans, and are even found the the same location in the genomes.

Another 17 lineages were not common to mysticetes and odontocetes, but are found in specific sub-lineages of cetaceans. This observation suggests that they were acquired from other non-cetacean mammals. In support of this hypothesis, it was found that these ERVs are closely to ERVs in a variety of land mammals including bats and cows. These ERVs are more numerous in the cetacean genome, implying that they entered recently and might still be infecting these mammals. Whether or not the infections have pathogenic consequences is unknown.

The reader might be asking how a whale might acquire a virus from terrestrial and semi-aquatic mammals. Apparently there is more interaction of cetaceans with these animals than we think: killer whales have been observed feeding on terrestrial mammals and seals.

Given the difficulty in sampling cetaceans, it will be difficult to determine how other viruses originated in these animals. This question can be readily addressed for endogenous retroviruses because they are integrated into germline DNA, often for millions of years.

Filed Under: Basic virology, Information Tagged With: cetacean, endogenous retrovirus, ERV, phylogenetic analysis, retrovirus, viral, virology, virus, viruses

Retroviruses and the placenta, a remarkable relationship

21 June 2019 by Vincent Racaniello

Retroviruses have been infecting vertebrates for over 450 million years. Because retroviral DNA integrates into host cell DNA, the vertebrate genome is littered with remnants of these infections. Some of this retroviral DNA has been co-opted by the cell for a variety of beneficial purposes, such as development of the placenta and the control of birth timing.

[Read more…] about Retroviruses and the placenta, a remarkable relationship

Filed Under: Basic virology, Information Tagged With: corticotropin-releasing hormone, endogenous retrovirus, ERV, placenta, retrovirus, syncytiotrophoblast, viral, virology, virus, viruses

Purging the PERVs

17 August 2017 by Vincent Racaniello

pigThere aren’t enough human organs to meet the needs for transplantation, so we have turned to pigs. Unfortunately pig cells contain porcine endogenous retroviruses, PERVS, which could infect the transplant recipient, leading to tumor formation. But why worry? Just use CRISPR to purge the PERVs.

The genomes of many species on Earth are littered with endogenous retroviruses. These are DNA copies of retroviral genomes from previous infections that are integrated into germ line DNA and passed from parent to offspring. About 8% of the human genome consists of ERVs. The pig genome is no different – it contains PERVs (an acronym made to play with). The genome of an immortalized pig cell line called PK15 contains 62 PERVs. Human cells become infected with porcine retroviruses when they are co-cultured with PK15 cells.

The presence of PERVS is an obvious problem for using pig organs for transplantation into humans – a process called xenotransplantation. The retroviruses produced by pig cells might infect human cells, leading to problems such as immunosuppression and tumor formation. No PERV has ever been shown to be transmitted to a human, but the possibility remains, especially with   the transplantation of increasing numbers of pig organs into humans.

The development of CRISPR/Cas9 gene editing technology made it possible to remove PERVs from pigs, potentially easing the fears of xenotransplantation. This technology was first used to remove all 62 copies of PERVS from the PK15 cell line. But having PERV-free pig cells doesn’t help humans in need of pig organs – for that you need pigs.

To make pigs without PERVs, CRISPR/Cas9 was used to remove the PERVs from primary (that is, not immortal) pig cells in culture. Next, the nuclei of these PERV-less cells was used to replace the nucleus of a pig egg cell. After implantation into a female, these cells gave rise to piglets lacking PERVs.

In theory such PERV-less piglets can be used to supply organs for human transplantation, eliminating the worrying about infecting humans with pig retroviruses. But first we have to make sure that the PERV-free pigs, and their organs, are healthy. The more we study ERVs, the more we learn that they supply important functions for the host. For example, the protein syncytin, needed to form the placenta, is a retroviral gene, and the regulatory sequences of interferon genes come from retroviruses. There are likely to be many more examples of essential functions provided by ERVs. It would not be a good idea to have transplanted pig organs fail because they lack an essential PERV!

Filed Under: Basic virology, Information Tagged With: CRISPR/Cas9, endogenous retrovirus, ERV, genome editing, PERV, pig, transplantation, viral, virology, virus, viruses, xenotransplantation

TWiV 439: The purloined envelope

30 April 2017 by Vincent Racaniello

Paul Bieniasz joins the TWiV team to talk about the co-option, millions of years ago, of an endogenous retrovirus envelope protein by hominid ancestors for host defense against viral infection.

 

You can find TWiV #439 at microbe.tv/twiv, or listen. below.

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Filed Under: This Week in Virology Tagged With: endogenous retrovirus, envelope protein, ERV, exaptation, gammareterovirus, HERV-T, hominid, MCT-1, Paul Bieniasz, retrovirus, viral, viral receptor, virology, virus, viruses

TWiV 386: The dolphins did it

24 April 2016 by Vincent Racaniello

TWiVDid you know that the evolution of ancient retroviruses, millions of years ago, can be traced by studying their genomes in the chromosomes of contemporary animals? Ted Diehl and Welkin Johnson join the TWiV team to tell us how they did it with mammals. All without a single wet experiment! They also join in the discussion about virus dispersal by hand dryers.

You can find TWiV #386 at microbe.tv/twiv, or listen below.

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Filed Under: This Week in Virology Tagged With: bacteriophage, cross-species infection, dyson hand dryer, endogenous retrovirus, ERV, hand drying, mammal, paleovirology, recombination, retrovirus, viral, virology, virus, virus dispersal, viruses

TWiV 382: Everyone’s a little bit viral

27 March 2016 by Vincent Racaniello

TWiVOn episode #382 of the science show This Week in Virology, Nels Elde and Ed Chuong join the TWiV team to talk about their observation that regulation of the human interferon response depends on regulatory sequences that were co-opted millions of years ago from endogenous retroviruses.

You can find TWiV #382 at microbe.tv/twiv, or listen below.

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Filed Under: This Week in Virology Tagged With: AIM, CHiP, computational biology, crispr, endogenous retroviruses, enhancer, ERV, IFN, inflammasome, interferon, retrovirus, STAT1, transposable element, viral, virology, virus, viruses

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