206 posts · 178,801 views
Immunology, virology, baseball, and pictures of my kids
We know that viruses cause a significant minority of human cancers, but we don’t know quite how many, or which, cancers are viral. It’s not as easy as you might think to tell.
The link between viruses and cancer was one of the major breakthroughs in cancer biology, but you could also make a case that [...]... Read more »
Feng, H., Shuda, M., Chang, Y., & Moore, P. (2008) Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma. Science, 319(5866), 1096-1100. DOI: 10.1126/science.1152586
Dworkin, A., Tseng, S., Allain, D., Iwenofu, O., Peters, S., & Toland, A. (2009) Merkel Cell Polyomavirus in Cutaneous Squamous Cell Carcinoma of Immunocompetent Individuals. Journal of Investigative Dermatology. DOI: 10.1038/jid.2009.183
Shuda, M., Feng, H., Kwun, H., Rosen, S., Gjoerup, O., Moore, P., & Chang, Y. (2008) T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus. Proceedings of the National Academy of Sciences, 105(42), 16272-16277. DOI: 10.1073/pnas.0806526105
Here we estimated the evolutionary history and inferred date of introduction to humans of each of the genes for all 20th century pandemic influenza strains. Our results indicate that genetic components of the 1918 H1N1 pandemic virus circulated in mammalian hosts, i.e., swine and humans, as early as 1911 and was not likely to be [...]... Read more »
Smith, G., Bahl, J., Vijaykrishna, D., Zhang, J., Poon, L., Chen, H., Webster, R., Peiris, J., & Guan, Y. (2009) From the Cover: Dating the emergence of pandemic influenza viruses. Proceedings of the National Academy of Sciences, 106(28), 11709-11712. DOI: 10.1073/pnas.0904991106
As if understanding this complex evolutionary puzzle were not already sufficiently challenging, we have learned recently that two types of adaptive immune system have evolved in vertebrates: a recently recognized system in jawless vertebrates (hagfish and lamprey) and the more familiar adaptive immune system of jawed vertebrates. … This leads to the conjecture that two [...]... Read more »
Leprosy is a fascinating disease for many reasons. Historical, because, well, it’s leprosy. Genetic, because the bacterium is apparently derived from a single clone that infected humans some 4000 years ago,1 and that has undergone “massive gene decay” in the process of becoming an obligate pathogen:
Thus, since diverging from the last common mycobacterial ancestor, the [...]... Read more »
Cole, S., Eiglmeier, K., Parkhill, J., James, K., Thomson, N., Wheeler, P., Honoré, N., Garnier, T., Churcher, C., Harris, D.... (2001) Massive gene decay in the leprosy bacillus. Nature, 409(6823), 1007-1011. DOI: 10.1038/35059006
Monot, M., Honoré, N., Garnier, T., Zidane, N., Sherafi, D., Paniz-Mondolfi, A., Matsuoka, M., Taylor, G., Donoghue, H., Bouwman, A.... (2009) Comparative genomic and phylogeographic analysis of Mycobacterium leprae. Nature Genetics, 41(12), 1282-1289. DOI: 10.1038/ng.477
(R. Carswell, 1831)
But despite these advances, there is far more that we simply do not understand about smallpox disease or its causative virus. The smallpox vaccine, vaccinia virus, remains the poster-child for human vaccines, but we have only begun to understand how vaccinia-induced immune responses protect vaccinees from orthopoxvirus infections. … In contrast, we [...]... Read more »
“Adenovirus” (by Mapposity) There are two aspects about virology that constantly amaze me: How much we know about viruses, and how little we know about viruses. Adenovirus research offers examples of both. Adenoviruses are probably among the best-studied virus groups.1 We really do know an amazing amount about them. But it was only last year [...]... Read more »
Zhang, Y., Huang, W., Ornelles, D., & Gooding, L. (2010) Modeling Adenovirus Latency in Human Lymphocyte Cell Lines. Journal of Virology, 84(17), 8799-8810. DOI: 10.1128/JVI.00562-10
Persons who were born before 1957 had a reduced risk of infection … Persons who were born between 1957 and 1975 were at intermediate risk for infection. 1
In Ontario, people over 53 years old had about 1/6 the chance2 of getting the new H1N1; the those between about 33 and 53 had a [...]... Read more »
David N. Fisman, Rachel Savage, Jonathan Gubbay, Camille Achonu, Holy Akwar, David J. Farrell, Natasha S. Crowcroft, & Phil Jackson. (2009) Older Age and a Reduced Likelihood of 2009 H1N1 Virus Infection. The New England Journal of Medicine, 2000-20001. info:/
“A terrified man realizing he has just contracted the plague, surrounded by a group of people.” By E.M. Ward, 1848. Even the most lethal pathogens we know of don’t kill every single infected individual.1. Sometimes this is because the pathogen that infects the person is relatively weak. Sometimes it’s because the dose was low. And [...]... Read more »
Centers for Disease Control and Prevention (CDC). (2011) Fatal Laboratory-Acquired Infection with an Attenuated Yersinia pestis Strain --- Chicago, Illinois, 2009. MMWR. Morbidity and mortality weekly report, 60(7), 201-5. PMID: 21346706
At this point in 2009, I think most people probably have a general grasp of influenza virus infection patterns. At the simplest level, a few strains of virus circulate every year, with relatively small changes year-to-year. Every so often, a new strain, with larger changes, appears and spreads globally, often becoming the dominant “base” [...]... Read more »
Worobey, M. (2008) Phylogenetic Evidence against Evolutionary Stasis and Natural Abiotic Reservoirs of Influenza A Virus. Journal of Virology, 82(7), 3769-3774. DOI: 10.1128/JVI.02207-07
Li, J., Dohna, H., Miller, J., Cardona, C., & Carpenter, T. (2009) Identifying errors in avian influenza virus gene sequences and implications for data usage of public databases. Genomics. DOI: 10.1016/j.ygeno.2009.09.005
Aquino, V., Amarilla, A., Alfonso, H., Batista, W., & Figueiredo, L. (2009) New Genotype of Dengue Type 3 Virus Circulating in Brazil and Colombia Showed a Close Relationship to Old Asian Viruses. PLoS ONE, 4(10). DOI: 10.1371/journal.pone.0007299
Dendritic cells in the skin (Langerhans cells) form a dense network of “sentinels” that act as first line of defense of the immune system.1
There’s a lot of interest in using dendritic cells as vaccines these days. A paper in PLoS One2 offers a cautionary note.
Dendritic cells (DC) are the main cell type that drive T [...]... Read more »
Yewdall, A., Drutman, S., Jinwala, F., Bahjat, K., & Bhardwaj, N. (2010) CD8 T Cell Priming by Dendritic Cell Vaccines Requires Antigen Transfer to Endogenous Antigen Presenting Cells. PLoS ONE, 5(6). DOI: 10.1371/journal.pone.0011144
I’ve talked about quasispecies several times, and emphasized that RNA viruses, with their high replication error rates, are most prone to forming quasispecies. I’ve also pointed out, though, that actually measuring quasispecies is technically difficult, and measuring it for the larger DNA viruses would be even harder. You’d need to run sequences on many viral [...]... Read more »
Cheng, T., Valentine, M., Gao, J., Pingel, J., & Yokoyama, W. (2009) Stability of Murine Cytomegalovirus Genome after In Vitro and In Vivo Passage. Journal of Virology, 84(5), 2623-2628. DOI: 10.1128/JVI.02142-09
TRegs in normal skin
Tumors are supposed to be destroyed by our immune system. So how come we still see tumors?
A big part of the answer is probably that our immune system is very good at destroying proto-tumors, but is not so good at handling those that manage to sneak through and grow to the [...]... Read more »
Zimring, J., & Kapp, J. (2004) Identification and Characterization of CD8 Suppressor T Cells. Immunologic Research, 29(1-3), 303-312. DOI: 10.1385/IR:29:1-3:303
Shafer-Weaver, K., Anderson, M., Stagliano, K., Malyguine, A., Greenberg, N., & Hurwitz, A. (2009) Cutting Edge: Tumor-Specific CD8 T Cells Infiltrating Prostatic Tumors Are Induced to Become Suppressor Cells. The Journal of Immunology, 183(8), 4848-4852. DOI: 10.4049/jimmunol.0900848
Anderson MJ, Shafer-Weaver K, Greenberg NM, & Hurwitz AA. (2007) Tolerization of tumor-specific T cells despite efficient initial priming in a primary murine model of prostate cancer. Journal of immunology (Baltimore, Md. : 1950), 178(3), 1268-76. PMID: 17237372
Confluent smallpox1 Vaccination against smallpox ended some 40 years ago. As the vaccinated population gets smaller and the susceptible population gets larger, at least one poxvirus is re-exploring the human population. Not smallpox, of course, but monkeypox, which is becoming dramatically more common in humans than it used to be.2 Monkeypox (which is actually primarily [...]... Read more »
Rimoin, A., Mulembakani, P., Johnston, S., Lloyd Smith, J., Kisalu, N., Kinkela, T., Blumberg, S., Thomassen, H., Pike, B., Fair, J.... (2010) Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo. Proceedings of the National Academy of Sciences, 107(37), 16262-16267. DOI: 10.1073/pnas.1005769107
Pierre Formenty, Mohammed O. Muntasir, Inger Damon, Vipul Chowdhary, Martin L. Opoka, Charlotte Monimart, Elmangory M. Mutasim, Jean-Claude Manuguerra, Whitni B. Davidson, Kevin L. Karem.... (2010) Human Monkeypox Outbreak Caused by Novel Virus Belonging to Congo Basin Clade, Sudan, 2005. Emerging Infectious Diseases, 16(10). info:/10.3201/eid1610.100713
Nalca, A., Livingston, V., Garza, N., Zumbrun, E., Frick, O., Chapman, J., & Hartings, J. (2010) Experimental Infection of Cynomolgus Macaques (Macaca fascicularis) with Aerosolized Monkeypox Virus. PLoS ONE, 5(9). DOI: 10.1371/journal.pone.0012880
Hutson CL, Lee KN, Abel J, Carroll DS, Montgomery JM, Olson VA, Li Y, Davidson W, Hughes C, Dillon M.... (2007) Monkeypox zoonotic associations: insights from laboratory evaluation of animals associated with the multi-state US outbreak. The American journal of tropical medicine and hygiene, 76(4), 757-68. PMID: 17426184
Highly pathogenic H5N1 influenza viruses possessing mammalian-type PB2-627 were detected during the Qinghai Lake outbreak in 2005 and spread to Europe and Africa. … Here, we report that H5N1 avian influenza viruses possessing mammalian-type amino acids in PB2-627 or -701 are selected during replication in ostrich cells in vitro and in vivo.
–Shinya, K., Makino, A., [...]... Read more »
Shinya, K., Makino, A., Ozawa, M., Kim, J., Sakai-Tagawa, Y., Ito, M., Le, Q., & Kawaoka, Y. (2009) Ostrich involvement in the selection of H5N1 influenza virus possessing mammalian-type amino acids in PB2. Journal of Virology. DOI: 10.1128/JVI.01714-09
From A History of British Fish (William Yarrell, 1835) I’ve talked about lamprey immune systems several times (here, here, and here). I find them fascinating because it shows both how our own immune system developed, and also shows alternate routes that can lead to a pretty good, but very different, immune system. Quick background: In [...]... Read more »
Herrin, B., & Cooper, M. (2010) Alternative Adaptive Immunity in Jawless Vertebrates. The Journal of Immunology, 185(3), 1367-1374. DOI: 10.4049/jimmunol.0903128
Human cytomegalovirus-infected cell
A number of viruses, especially herpesviruses, block the MHC class I antigen presentation system. It’s been widely assumed that this is for the obvious reason and that it allows the virus to avoid T cell recognition and elimination. But there’s been an awkward lack of experimental support for that assumption, to [...]... Read more »
Hansen, S., Powers, C., Richards, R., Ventura, A., Ford, J., Siess, D., Axthelm, M., Nelson, J., Jarvis, M., Picker, L.... (2010) Evasion of CD8 T Cells Is Critical for Superinfection by Cytomegalovirus. Science, 328(5974), 102-106. DOI: 10.1126/science.1185350
The huge 1918 influenza pandemic, caused by the great-grandfather of today’s swine-origin pandemic H1N1, wasn’t the first time influenza was seen in people — not by a couple of thousand years. 1 Seasonal flu was around before it, just as it has been since; and epidemics and pandemics regularly swept through the world before 1918.
The charts [...]... Read more »
Warren T. Vaughn. (1921) Influenza: An Epidemiologic Study. The American Journal of Hygiene Monographic Series. info:/
A truly amazing paper in today’s Nature1 shows 2-photon microscopy videos of T cells entering the brain in search of their target antigen. The title of this post is taken from the commentary,2 also in Nature.
Disease-causing T cells first adhere to the inner walls of the pial vessels and then crawl in continuous contact with [...]... Read more »
Bartholomäus, I., Kawakami, N., Odoardi, F., Schläger, C., Miljkovic, D., Ellwart, J., Klinkert, W., Flügel-Koch, C., Issekutz, T., Wekerle, H.... (2009) Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions. Nature, 462(7269), 94-98. DOI: 10.1038/nature08478
Needleman et al, 1 Fig 1: Section of rat vidual cortext stained for MHC class I (green) and nuclei (red) Needleman et al, 1 Fig 1: Section of rat vidual cortext stained for MHC class I (green) and nuclei (red) I said the other day that not all MHC class I molecules are involved in immunity, and [...]... Read more »
Needleman, L., Liu, X., El-Sabeawy, F., Jones, E., & McAllister, A. (2010) MHC class I molecules are present both pre- and postsynaptically in the visual cortex during postnatal development and in adulthood. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1006087107
Goddard, C., Butts, D., & Shatz, C. (2007) Regulation of CNS synapses by neuronal MHC class I. Proceedings of the National Academy of Sciences, 104(16), 6828-6833. DOI: 10.1073/pnas.0702023104
Zohar O, Reiter Y, Bennink JR, Lev A, Cavallaro S, Paratore S, Pick CG, Brooker G, & Yewdell JW. (2008) Cutting edge: MHC class I-Ly49 interaction regulates neuronal function. Journal of immunology (Baltimore, Md. : 1950), 180(10), 6447-51. PMID: 18453559
Goddard CA, Butts DA, & Shatz CJ. (2007) Regulation of CNS synapses by neuronal MHC class I. Proceedings of the National Academy of Sciences of the United States of America, 104(16), 6828-33. PMID: 17420446
Huh, G. (2000) Functional Requirement for Class I MHC in CNS Development and Plasticity. Science, 290(5499), 2155-2159. DOI: 10.1126/science.290.5499.2155
TRegs infiltrate into a tumor There’s increasing evidence supporting the notion that tumors are often not rejected by the immune system because regulatory T cells actively block the immune response to the tumor cells. 1 That means that within the tumor, two branches of the immune response are fighting it out. If the TRegs win, [...]... Read more »
Kuczma, M., Kopij, M., Pawlikowska, I., Wang, C., Rempala, G., & Kraj, P. (2010) Intratumoral Convergence of the TCR Repertoires of Effector and Foxp3 CD4 T cells. PLoS ONE, 5(10). DOI: 10.1371/journal.pone.0013623
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