TWiV 374: Discordance in B

TWiVOn episode #374 of the science show This Week in Virology, the TWiVniks consider the role of a cell enzyme that removes a protein linked to the 5′-end of the picornavirus genome, and the connection between malaria, Epstein-Barr virus, and endemic Burkitt’s lymphoma.

You can find TWiV #374 at microbe.tv/twiv.

TWiP 31: A malaria vaccine

p.falciparum life cycleHosts: Vincent Racaniello and Dickson Despommier

Vincent and Dickson discuss the promising results of a phase III trial of a malaria vaccine in African children.

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TWiP 28: Medical entomology with Robert W. Gwadz

anopheles gambiaeHosts: Vincent Racaniello and Dickson Despommier

On episode #28 of the podcast This Week in Parasitism, Vincent and Dickson discuss medical entomology with Robert W. Gwadz, Assistant Chief of the Laboratory of Malaria and Vector Research at NIAID.

Click the arrow above to play, or right-click to download TWiP #28 (65 MB .mp3, 91 minutes).

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TWiP #28 (65 MB .mp3, 91 minutes)

Dickson Despommier’s Parasitic Diseases lectures

dickson despommierProfessor Dickson Despommier, co-host of TWiV and TWiP, and well known for his ideas about vertical farming, taught parasitology to medical, dental, and nursing students at Columbia University’s College of Physicians & Surgeons for 38 years. Below are videocasts of the six lectures from the final version of his course, Parasitic Diseases, which he taught in the fall of 2009. These are excellent companions to the first 27 episodes of TWiP, which explore the basics of eukaryotic parasites including protozoa, nematodes, cestodes, and trematodes.

Parasitic Diseases Fall 2009 – videocasts
To download the files, right-click on the link and save-as.

Lecture 1: Nematodes I – Enterobius, Trichuris, Ascaris, Toxocara (19 MB .mov)
Lecture 2: Nematodes II – Hookworm, Strongyloides (18 MB .mov)
Lecture 3: Cestodes – Taenia, Echinococcus (Joshua Stillman, MD) (19 MB .mov)
Lecture 4: Trematodes – Schistosoma (17 MB .mov)
Lecture 5: The Malarias (19 MB .mov)
Lecture 6: Protozoa – Giardia, Entamoeba, Cryptosporidium, Cyclospora (16 MB .mov)

TWiV 115: Color me infected

brainbow pseudorabies virusHosts: Vincent RacanielloAlan DoveRich Condit, and Marc Pelletier

On episode #115 of the podcast This Week in Virology, Vincent, Alan, Rich and Marc discuss the finding that a limited number of incoming herpesviral genomes can replicate and express in a cell, and controlling viral replication in Aedes aegypti with a Wolbachia symbiont.

Click the arrow above to play, or right-click to download TWiV #115 (84 MB .mp3, 117 minutes).

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Weekly Science Picks

Marc – Homebrew bioreactor (photo, movie) – culture bottle and drive, oil-free vacuum pumps
Rich –
Logitech Harmony Universal Remote
Alan – H.M.S. Challenger Reports
Vincent – Sequence of the strawberry genome and blog post by lead author

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

TWiP 11: One times three million

Hosts: Vincent Racaniello and Dickson Despommier

On episode 11 of the podcast “This Week in Parasitism”, Vincent and Dickson continue their discussion of malaria, with emphasis on clinical aspects of the disease.

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TWiP is brought to you by the American Society for Microbiology at Microbeworld.org.

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Download TWiP #11 (63 MB .mp3, 87 minutes)

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TWiP 10: Plasmodium life cycle

Hosts: Vincent Racaniello and Dickson Despommier

On episode 10 of the podcast “This Week in Parasitism”, Vincent and Dickson trace the life cycle of Plasmodium in a mosquito and in a human host.

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TWiP is brought to you by the American Society for Microbiology at Microbeworld.org.

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  • Mosquito cycle – sporogany (jpg)
  • Plasmodium falciparum cycle (jpg)
  • Plasmodium vivax cycle (jpg)
  • Plasmodium falciparum ring forms and gametocytes in blood (jpg)
  • Plasmodium stages (jpg)
  • Letters read on TWiP 10

Download TWiP #10 (62 MB .mp3, 86 minutes)

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TWiP 9: Mala aria

Hosts: Vincent Racaniello and Dickson Despommier

On episode 9 of the podcast “This Week in Parasitism”, Vincent and Dickson move on to protozoan parasites with a discussion of the early history of malaria..

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TWiP is brought to you by the American Society for Microbiology at Microbeworld.org.

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Download TWiP #9 (59 MB .mp3, 82 minutes)

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Polyomavirus JC, multiple sclerosis, Tysabri, and an anti-malaria drug

mefloquineBiogen has announced that an anti-malaria compound may be useful for treating a brain infection, progressive multifocal leukoencephalopathy (PML), that is an adverse effect of the company’s multiple sclerosis/Crohn’s disease drug Tysabri. How does JC virus fit into this story?

Tysabri is the trade name for Natalizumab, a monoclonal antibody against the cellular protein alpha-4 integrin. The antibody was approved by the US Food and Drug Administration for the treatment of multiple sclerosis and Crohn’s disease. Both are autoimmune diseases in which the immune system damages host tissues. In multiple sclerosis, the immune system attacks the central nervous system, causing loss of the myelin sheath that surrounds neurons – also known as demyelination. As a consequence, nerve function is impaired, leading to physical and cognitive deterioration. In Crohn’s disease, immune cells damage the gastrointestinal tract, which causes severe pain, diarrhea, vomiting, and weight loss. The membrane protein alpha-4 integrin is important in the movement of immune cells from the bloodstream into surrounding tissues. Treatment with an antibody to this protein is believed to inhibit such cell movement, thereby decreasing the immune attack in multiple sclerosis and Crohn’s disease.

Tysabri is an immunosuppressive drug, and the problem with treating any illness with such a compound is that opportunistic infections may occur. Indeed, shortly after Tysabri was approved, several cases of progressive multifocal leukoencephalopathy occurred in recipients of the drug. This is a rare and usually fatal neurological disease caused by the polyomavirus JC. The virus multiplies in and destroy oligodendrocytes, which are cells of the brain that produce the myelin sheath surrounding neurons. JCV was identified in 1971 by inoculation of brain material from a PML patient into cultured human fetal glial cells. In the same year, another polyomavirus, BK, was isolated from the urine of a human renal transplant patient.

Both JCV and BKV are widespread in humans: it has been estimated that up to 90% of the global population is infected with these viruses. Most infections are asymptomatic, making it difficult to determine how the virus is transmitted. They are probably shed intermittently throughout life and spread to others by respiratory or oral routes. Why these viruses can persist for long periods in humans without causing disease is a mystery.

When patients are immunosuppressed – for organ transplantation, as a consequence of AIDS, or by treatment with Tysabri or other monoclonal antibodies that dampen the host immune response – JCV  may multiply unchecked and cause PML. These observations tell us that the immune system is important in regulating the asymptomatic nature of  human polyomavirus infections.

MS is a relatively common disease (incidence 2-150 per 100,000 population) and therefore treatments such as Tysabri are extremely useful. Clearly it was important for Biogen to determine how to limit the incidence of PML in patients receiving this antibody. Screening a chemical library of 2000 FDA-approved drugs identified mefloquine as an inhibitor of JCV. This compound is now being tested in humans for treatment of PML.

Other human polyomaviruses, including Li, WU, and Merkel cell virus, have been identified in human samples. As immunosuppressive therapy becomes more commonly used to treat a variety of human illnesses, these and other yet undiscovered viruses are likely to emerge as new pathogenic agents. We do not know how many different viruses colonize humans without causing disease. But it is safe to conclude that the zoonotic pool is not the only source of new virus infections for us to worry about.

Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, & Dessel BH. (1971). Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet, 19, 1257-1260 PMID: 4104715

Gardner SD, Field AM, Coleman DV, & Hulme B. (1971). New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet, 19, 1253-1257 PMID: 4104714

Brickelmaier, M., Lugovskoy, A., Kartikeyan, R., Reviriego-Mendoza, M., Allaire, N., Simon, K., Frisque, R., & Gorelik, L. (2009). IDENTIFICATION AND CHARACTERIZATION OF MEFLOQUINE EFFICACY AGAINST JC VIRUS IN VITRO Antimicrobial Agents and Chemotherapy DOI: 10.1128/AAC.01614-08

TWiV #24: Viroids

twiv_aa_2001In episode #24 of the podcast This Week in Virology, Vincent, Alan, and Hamish Young discuss bacteriophages in viral vaccines, enteroviruses and diabetes, inhibition of Hendra and Nipah virus replication by the malaria drug chloroquine, and viroids.

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