Mabuya mabouyaThe protein syncytin, which is essential for formation of the placenta, originally came to the genome of our ancestors, and those of other mammals, via a retrovirus infection. Placental structures have also developed in non-mammalian vertebrates. The Mabuya lizard (pictured: image credit), which emerged 25 million years ago, has a placenta very much like those in mammals, and its development was likely driven by capture of a retroviral gene.

The genetic material of retroviruses is RNA, but during infection it is converted to DNA which then integrates into the chromosome of the cell.  If the infected cell happens to be a germ cell, then the viral DNA, now called called an endogenous retrovirus, becomes a permanent part of the animal and its offspring. One of the retroviral genes, env, encoding the viral glycoprotein, has been repurposed by mammals to become the syncytin genes. These encode fusogenic proteins that are involved in the formation, by cell-cell fusion, of the syncytiotrophoblast.

Syncytins are present in all placental mammals, leading to the hypothesis that retroviral infection has driven the evolution of placental mammals from egg laying species.

Placentas are not limited to mammals – they emerged in other vertebrates, including in certain lizards in the family Scincidae. In one genus, Mabuya, (pictured), the placenta is structurally similar to the mammalian placenta.

Examination of placental RNA from the Mabuya lizard revealed the presence of transcripts from retroviral-like env genes. They are part of  ancient retroviral genomes integrated in the lizard genome. The encoded proteins are synthesized in the placenta, and are fusogenic – they can cause fusion cells in which they are produced. The receptor for these lizard syncytins was identified, and shown to be also present in the placenta.

The first placenta-like structures probably arose in egg-laying vertebrates, around 400 million years ago in fish, 150 million years ago in mammals, and 25 million years ago in Mabuya lizards. It seems likely that these events took place after retrovirus infection followed by capture of env genes, which allowed fusion of cells in the placenta. This repurposing of a retroviral gene occurred randomly and rarely in evolution, but it clearly imposed an advantage, as placental-mediated live birthing has endured.

Without retroviruses, many species might still be laying eggs – and that includes humans.

By David Tuller, DrPH

So let’s talk about Professor Esther Crawley’s SMILE trial, published in September by the journal Archives of Disease in Childhood, one of the BMJ Publishing Group’s titles. The study reported that a commercial intervention called the Lightning Process was an effective treatment for children with CFS/ME when offered along with what was called “specialist medical care.”

[click to continue…]

The TWiVerinos discuss restriction of dengue virus vaccine by Sanofi, and data which suggest that Dengvaxia causes enhanced disease in previously uninfected recipients.

Click arrow to play
Download TWiV 471 (66 MB .mp3, 108 min)
Subscribe (free): iTunesRSSemail

Become a patron of TWiV!

Show notes at microbe.tv/twiv

DengvaxiaA dengue virus vaccine was recently developed not only to prevent first infections, but to avoid severe disease that may occur upon second and third infections. This consequence, called antibody dependent enhancement (ADE), now appears to be caused by the vaccine itself.

[click to continue…]

By David Tuller, DrPH

Well, last week was certainly exciting! As I wrote on Wednesday, I was planning to post about Professor Esther Crawley’s SMILE trial. However, that plan changed when Sue Paterson, the University of Bristol’s director of legal services, e-mailed me what I guess was supposed to be a scary letter.

The letter pointedly cited the “close and valued collaborative relationship” between Bristol and Berkeley, which is of no concern to me and has zero relevance to the current situation. Then, in referencing “private and confidential communication” at “a senior level,” Ms. Paterson appeared to be making ominous insinuations about potential professional payback for my “actions and behaviour” toward Bristol personnel involved in ME/CFS research. (That would presumably be Professor Crawley.)

[click to continue…]

The TWiV ninjas reveal that bacteriophage particles rapidly move across monolayers of eukaryotic cells from different tissues.

Click arrow to play
Download TWiV 470 (71 MB .mp3, 117  min)
Subscribe (free): iTunesRSSemail

Become a patron of TWiV!

Show notes at microbe.tv/twiv

The influenza virus vaccine is frequently updated to ensure that it protects against infection with circulating virus strains. In some years the vaccine matches the circulating strains, but in others, there is a mismatch. The result is that the vaccine is less effective at protecting from infection. During the 2014-15 influenza season there was a mismatch due to growing the vaccine in embryonated chicken eggs.

[click to continue…]

By David Tuller, DrPH

Update: About 20 minutes after posting this blog, I received the following communication from Ms. Paterson:

Dear Dr Tuller

Thank you for your email of 22 November.

If by a ‘cease and desist’ letter you mean a letter threatening legal action if the recipient does not stop a specified activity or behaviour, then I can confirm that the University of Bristol has not sent you or your institution such a letter.

However you will be aware that the University of Bristol has for many years enjoyed a close and valued collaborative relationship with the University of California, Berkeley, and it is my understanding that private and confidential communication has taken place at a senior level about your actions and behaviour towards staff involved with research into chronic fatigue syndrome and myalgic encephalomyelitis at the University of Bristol.

Yours sincerely
Sue Paterson

I note that this message from Ms. Paterson confirms that Professor Crawley’s statement about Bristol sending me a cease and desist letter is not true. I also note that it contains no evidence or documentation that anything I have written is inaccurate or in error, and that Professor Crawley has still not taken me up on my offers to correct any mistakes and post her full comment on Virology Blog.

I have not responded to Ms. Paterson at this point. I await further developments with interest.

**********

Bristol University has an Esther Crawley problem. A week ago, I e-mailed Sue Paterson, Bristol’s director of legal services, asking her to clarify as soon as possible whether the university had sent me a cease and desist letter. Professor Crawley made such a claim in a November 17th talk at the University of Exeter, in response to my question about why she had accused me of libel and then refused to provide evidence that anything I wrote was in error. Her statement about this issue was clear and unambiguous: “You have been so unbelievably defamatory and unprofessional that I had to get my university to send you a cease and desist letter,” she said.

[click to continue…]

The TWiV hosts discuss a plant virus that infects a fungus, and whether you need to work insane hours to succeed in science.

Click arrow to play
Download TWiV 469 (66 MB .mp3, 108 min)
Subscribe (free): iTunesRSSemail

Become a patron of TWiV!

Show notes at microbe.tv/twiv

Cindy, Steph, and Vincent reveal that lymphocyte trafficking through lymph nodes and lymph is circadian – it is dependent on the time of day.

Click arrow to play
Download Immune 2 (53 MB .mp3, 87 min)
Subscribe (free): iTunesRSSemail

Become a patron of Immune!

Show notes at microbe.tv/immune