TWiV 280: Post viral

On episode #280 of the science show This Week in Virology, the TWiVmeisters answer listener email about the NEIDL, negative results, patenting MERS-coronavirus, human papillomavirus transmission, canine distemper virus, and much, much more.

You can find TWiV #280 at www.microbe.tv/twiv.

Harald zur Hausen on human papillomaviruses

I interviewed Harald zur Hausen, MD., recipient of the 2008 Nobel Prize in Physiology or Medicine, in Manchester UK at the 2013 meeting of the Society for General Microbiology. We spoke about his career, his work leading to the discovery that human papillomavirus types 16 and 18 are causative agents of cervical cancer, and his thoughts on other agents of human cancers.

TWiV 164: Six steps forward, four steps back

xmrvHosts: Vincent RacanielloRich Condit, and Alan Dove

Vincent, Alan, and Rich review ten compelling virology stories of 2011.

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Click the arrow above to play, or right-click to download TWiV 164 (60 MB .mp3, 99 minutes).

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Ten virology stories of 2011:

  1. XMRV, CFS, and prostate cancer (TWiV 119, 123, 136, 150)
  2. Influenza H5N1, ferrets, and the NSABB (TWiV 159)
  3. The Panic Virus (TWiV 117)
  4. Polio eradication (TWiV 127, 149)
  5. Viral oncotherapy (TWiV 124, 131, 142, 156)
  6. Hepatitis C virus (TWiV 130, 137, 141)
  7. Zinc finger nuclease and HIV therapy (TWiV 144)
  8. Bacteria help viruses (TWiV 154)
  9. Human papillomaviruses (TWiV 126)
  10. Combating dengue with Wolbachia (TWiV 115, 147)

Links for this episode:

Weekly Science Picks

Rich – Fundamentals of Molecular Virology by Nicholas H. Acheson
AlanFetch, with Ruff Ruffman
Vincent – Year end reviews at Rule of 6ix and Contagions

Listener Pick of the Week

GarrenTrillion-frame-per-second video
Judi – iBioMagazine
Ricardo –
Brain Picking’s 11 best science books of 2011

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

TWiV 151: Dear TWiVers

viral mailHosts: Vincent Racaniello, Alan Dove, and Rich Condit

Vincent, Alan, and Rich review questions and comments from TWiV listeners

Click the arrow above to play, or right-click to download TWiV 151 (49 MB .mp3, 81 minutes).

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Links for this episode:

Weekly Science Picks

Alan – Aurora Australis from space
Vincent –
Science360 Radio
Rich – 
Ghost Productions (demo and website)

Listener Pick of the Week

SophieBacteria by Jonathan Coulton

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

TWiV 150: Contaminated

pXMRVHosts: Vincent RacanielloRich Condit, and Dickson Despommier

Vincent, Dickson, and Rich meant to do an all-email episode, but first they review results of the Blood XMRV Scientific Research Working Group, and partial retraction of the paper associating XMRV with chronic fatigue syndrome.

With this episode TWiV is three years old.

Click the arrow above to play, or right-click to download TWiV 150 (56 MB .mp3, 93 minutes).

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, by email, or listen on your mobile device with the Microbeworld app.

Links for this episode:

Weekly Science Picks

Dickson – The Tree of Life
Vincent –
When do you fact-check article content with sources? (take as directed)
Rich –
io9

Listener Pick of the Week

LuisNIH videocasting and podcasting

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

Women AND men beware: HPV, the culprit behind more than just cervical cancers?

gardasilThis article was written for extra credit by a student in my virology course.

by Bethany DiPrete

Human papillomavirus (HPV) infection is the most common sexually transmitted disease in the United States, and as of yet, there is no cure.  However, there is a vaccine to prevent infection by certain strains. Recent research may encourage not just the young women of the world, but also the men, to rush to their doctors for this vaccine. As the advertisements for Gardasil have taught many of us, certain strains of HPV are responsible for the majority of cervical cancer cases. Now research is uncovering HPV as a major factor in several oral cancers as well. While men may have thought there was no need to get vaccinated against HPV before, this new information may change things.

Human papillomavirus infects epithelial cells of skin and mucous membranes. Through skin abrasions caused by injury or sexual contact, the virus gains access to the basal layer of the epithelial tissue, which is the lowest layer of the skin. HPV is a DNA virus that replicates in the epithelium at the primary site of infection. Noncancerous strains, which cause papillomas (warts) or even no apparent symptoms, replicate in the basal epithelial cells. The viral genome does not integrate into the host genome of the cell it infects, but instead replicates autonomously in a dividing cell. The productivity of viral replication depends on the stage of cell differentiation. As the infected cell moves to the upper level of the epithelium and begins to differentiate, viral replication becomes more productive. Replication producing high concentrations of viral genomes and the assembly of new virus particles (virions) is restricted to the outer epithelial cells, which are fully differentiated and no longer divide.

In cancers caused by viral infection, the virus must transform the infected cell, changing its growth properties and allowing for progression to cancer. In transformed cells, the viral genome has integrated into the host genome. When the viral DNA is integrated into the cellular genome, the viral mRNA that is then transcribed can contain cellular DNA sequences and is subsequently more stable than sequences transcribed from a nonintegrated viral genome. Because the mRNA transcripts are more stable, viral proteins, specifically proteins E6 and E7, are present in higher concentrations than in cells where the viral genome is not integrated. These viral proteins E6 and E7 interfere with the cell cycle by restricting the activity of the cellular tumor suppressor proteins p53 and Rb. Specifically, E6 blocks apoptosis (programmed cell death) by inducing degradation of p53. In an uninfected cell, proteins Rb and p53 sense DNA damage and prevent the cell cycle from progressing further. Protein E7 binds Rb proteins, allowing the cell replication cycle to progress so the virus can replicate. Once a cell has been transformed, the cell replication cycle goes unchecked and this can allow for the accumulation of mutations in the cell’s DNA. This buildup of mutations and frequent cellular replication can lead to oncogenesis, the development of cancer. The specific strains that are associated with these changes in epithelial tissue that can lead to cancer are strains 16 and 18. These are the strains from which Gardasil protects an individual, along with strains 6 and 11, which cause genital warts.

Researchers have studied oral cancers among men who are nonsmokers and nondrinkers, and discovered the presence of HPV in the biopsied tissues. In fact, some researchers are now claiming that the prevalence of HPV induced oral cancers is greater than cancers caused by both smoking and drinking combined. HPV is spread by direct skin-to-skin contact and sexual contact, and its replication is localized to the site of infection. Therefore, individuals who do not engage in vaginal intercourse, but do engage in other forms of sexual contact, such as oral sex, are still at risk for HPV infection. Virus is shed from the epithelial cells of the infected individual, even when the individual is asymptomatic. If an individual is orally infected with one of the high-risk strains (either 16 or 18), the virus will replicate locally in the infected tissue, and as described above, can cause cell transformation, leading to oncogenesis and tumor progression. Because of these risks, the importance of this vaccine for both men and women is becoming blatantly apparent.

Hocking JS, Stein A, Conway EL, Regan D, Grulich A, Law M, & Brotherton JM (2011). Head and neck cancer in Australia between 1982 and 2005 show increasing incidence of potentially HPV-associated oropharyngeal cancers. British journal of cancer, 104 (5), 886-91 PMID: 21285981

TWiV 135: Live in the Big Easy

ASM GM New OrleansHosts: Vincent Racaniello, Roger Hendrix, Rachel Katzenellenbogen, and Harmit Malik

Vincent and guests Rachel Katzenellenbogen, Roger Hendrix, and Harmit Malik recorded TWiV #135 live at the 2011 ASM General Meeting in New Orleans, where they discussed transformation and oncogenesis by human papillomaviruses, the amazing collection of bacteriophages on the planet, and the evolution of genetic conflict between virus and host.

Click the arrow above to play, or right-click to download TWiV #135 (63 MB .mp3, 97 minutes).

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Links for this episode:

 

Weekly Science Picks

Roger – Atomic structure of adenovirus by cry0-EM (Science)
Harmit
Syncytin knockout mice show role for endogenous retroviral gene (PNAS)
Vincent – Free science, one paper at a time by David Dobbs

Listener Pick of the Week

Mark  – Shot by Shot

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

TWiV 126: Wart’s up, doc?

michelle ozbunHosts: Vincent Racaniello, Dickson DespommierAlan DoveRich Condit, and Michelle Ozbun

On episode #126 of the podcast This Week in Virology, virologist Michelle Ozbun and the TWiV team review the biology of human papillomaviruses.

Click the arrow above to play, or right-click to download TWiV #126 (69 MB .mp3, 96 minutes).

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, by email, or listen on your mobile device with the Microbeworld app.

Links for this episode:

Weekly Science Picks

Michelle – HIV-1 utilizes chemokine receptor CXCR4 to enter stem cells (PubMed)
Dickson – Bengladesh bans sale of palm sap (NY Times)
Rich – The Medusa and the Snail by Lewis Thomas (“On Warts” – pdf)
Alan – Planting Science – students, teachers, and scientists collaborate on botany experiments
Vincent – CIDRAP – Center for Disease Research and Policy

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

TWiV 53: The ends justify the means

twiv-200Hosts: Vincent Racaniello, Dick Despommier, and Alan Dove

In episode #53 of the podcast “This Week in Virology”, Vincent, Dick, and Alan talk about Nobel prizes for telomere research, bacteriophages that protect aphids from wasps, salicylates and pandemic influenza mortality, and hand washing.

Click the arrow above to play, or right-click to download TWiV #53 (45 MB .mp3, 62 minutes)

Subscribe to TWiV in iTunes, by the RSS feed, or by email

Links for this episode:

Weekly Science Picks
Alan scienceline
Dick Younger by Judith Sulzberger MD
Vincent FluView

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv or leave voicemail at Skype: twivpodcast. You can also send articles that you would like us to discuss to delicious and tagging them with to:twivpodcast.

A plethora of papillomaviruses

human-papilloma-virusWhen Harald zur Hausen identified the first human papillomavirus (HPV-16) in 1983 in women with cervical cancer, little did he know he would receive the Nobel Prize in Medicine for this discovery 25 years later. He probably also did not know how difficult it would be to propagate these viruses in a way that would allow studies of all aspects of viral replication. A new method now allows the production of large quantities of virions which should permit new studies of the viral life cycle.

When the HPV dsDNA genome is introduced into primary human keratinocytes (PHKs), a small amount of DNA replication occurs but no infectious virus is produced. To circumvent this limitation, organotypic cell cultures called rafts were developed which enabled studies on viral replication. Raft cultures are prepared by plating PHKs on a collagen matrix containing fibroblasts; when placed at a liquid-air interface, the PHKs differentiate into a squamous epithelium. HPV replication can be studied in such cells after transfection of viral DNA, but the yields of virus particles are very low, and they cannot infect fresh cells.

In the new system, a plasmid carrying the HPV-18 DNA genome flanked by lox P sites is transfected into PHKs with a second plasmid that produces the Cre recombinase. This endonuclease cleaves the lox P sites, releasing the HPV genome from the plasmid, and viral DNA replication ensues. The cells produce high titers of progeny virus which can be used to infect fresh PHK cultures. The authors used this system to determine that viral DNA replication cannot take place while the cell is duplicating its own genome. Viral infection leads to a cessation of host DNA replication, at which time the cellular machinery is hijacked for the copying of viral genomes.

You might be wondering how the two HPV vaccines on the market, Gardasil (quadrivalent, types 6, 11, 16, 18) and Cervarix (bivalent, types 16 and 18) are produced, since their development pre-dates the high efficiency system described here. These vaccines consist of virus-like particles (VLPs), which are empty capsids that lack viral nucleic acids. The vaccines are produced by expressing in cells the viral capsid protein L1, which spontaneously assembles to form VLPs.

H.-K. Wang, A. A. Duffy, T. R. Broker, L. T. Chow (2009). Robust production and passaging of infectious HPV in squamous epithelium of primary human keratinocytes Genes & Development, 23 (2), 181-194 DOI: 10.1101/gad.1735109

D. A. Galloway (2009). Human papillomaviruses: a growing field Genes & Development, 23 (2), 138-142 DOI: 10.1101/gad.1765809