206 posts · 242,359 views
Immunology, virology, baseball, and pictures of my kids
The 1918 influenza pandemic that killed between 20 million and 100 million people world-wide was unusual in a lot of ways. One of the most extraordinary things about it was not just the high mortality rate, but the mortality pattern. Normally influenza kills the very old and the very young; but the 1918 [...]... Read more »
Laurel Yong-Hwa Lee, Do Lien Anh Ha, Cameron Simmons, Menno D. de Jong, Nguyen Van Vinh Chau, Reto Schumacher, Yan Chun Peng, Andrew J. McMichael, Jeremy J. Farrar, Geoffrey L. Smith.... (2008) Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals. Journal of Clinical Investigation. DOI: 10.1172/JCI32460
Polio patient in iron lung (1949)
It’s well known that HIV mutates rapidly and continuously in infected people. An individual is infected with a handful of HIV viruses, but quickly becomes the host of a vast cloud of virus genomes, with the dominant strain of HIV evolving over time.
There are several factors selecting which HIV [...]... Read more »
J. K. Odoom, Z. Yunus, G. Dunn, P. D. Minor, & J. Martin. (2008) Changes in Population Dynamics during Long-Term Evolution of Sabin Type 1 Poliovirus in an Immunodeficient Patient. Journal of Virology, 82(18), 9179-9190. DOI: 10.1128/JVI.00468-08
I’m marking final exams for the grad immunology class I teach, so I don’t have a lot of time to blog. But I do want to point to a really amazing, ambitious, and potentially world-changing initiative that doesn’t seem to have got the attention it deserves in the blog-world. A couple of ... Read more »
J APONTE, P AIDE, M RENOM, I MANDOMANDO, Q BASSAT, J SACARLAL, M MANACA, S LAFUENTE, A BARBOSA, & A LEACH. (2007) Safety of the RTS,S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique: a double blind randomised controlled phase I/IIb trial. The Lancet, 370(9598), 1543-1551. DOI: 10.1016/S0140-6736(07)61542-6
A couple of years ago, Jürg Tschopp’s group showed that uric acid crystals acted as inflammatory agents (and probably, also as adjuvants) by stimulating the Nalp3 inflammasome.1 A month ago, Richard Flavell’s group showed that alum adjuvant — also (sort of) crystalline — also acts through the Nalp3 inflammasome.2 And now, a paper ... Read more »
S Cassel, S C Eisenbarth, S S Iyer, J J Sadler, O R Colegio, L A Tephly, A B Carter, P B Rothman, R A Flavell, & F S Sutterwala. (2008) The Nalp3 inflammasome is essential for the development of silicosis. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.0803933105
Autoimmunity is surprisingly common, and amazingly complex. About 5% of people will develop some form of autoimmune disease — that’s tens of millions of people in North America alone — yet the causes underlying the diseases are still not known. It’s clear that there are both genetic and non-genetic factors, because if one ... Read more »
A while ago I talked about evolution of the herpesviruses, and I said:
We know of 200-odd herpesviruses so far, and more are being identified practically daily. It’s likely that virtually every animal species has its own set of unique herpesviruses. This is probably because herpesviruses are very host-restricted (rarely infecting more than a single species) ... Read more »
B Ehlers, G Dural, N Yasmum, T Lembo, B de Thoisy, M-P Ryser-Degiorgis, R Ulrich, & D McGeoch. (2008) Novel mammalian herpesviruses and lineages within the Gammaherpesvirinae: Cospeciation and interspecies transfer. Journal of Virology. DOI: 10.1128/JVI.02646-07
I’m not so much an antibody guy, but of course I’ve heard about catalytic antibodies. Catalytic antibodies bind, with the very high affinity that’s typical of many antibodies, to transition state molecules, stabilizing the transition state and facilitating the chemical reaction. They’ve been around for quite a while (I think the first, ... Read more »
E Hifumi, F Morihara, K Hatiuchi, T Okuda, A Nishizono, & T Uda. (2007) Catalytic Features and Eradication Ability of Antibody Light-chain UA15-L against Helicobacter pylori. Journal of Biological Chemistry, 283(2), 899-907. DOI: 10.1074/jbc.M705674200
Where did herpesviruses come from?
Humans, of course, have 8 different herpesviruses that are remarkably good at infecting us. Humans aren’t exceptional: We know of 200-odd herpesviruses so far, and more are being identified practically daily. It’s likely that virtually every animal species has its own set of unique herpesviruses. This is probably because herpesviruses are ... Read more »
C Farley, W G Banfield, G Jr Kasnic, & W A Foster. (1972) Oyster herpes-type virus. . Science, 178(62), 759-760.
HIV budding from a macrophage
The STEP anti-HIV vaccine trial received a lot of press coverage last year, when the vaccine was pulled for fear that it actually worsened HIV disease. A number of mechanisms were proposed for the exacerbation. One of those has now received some support.1
The STEP study used adenovirus vectors, expressing HIV proteins, to induce [...]... Read more »
M. Perreau, G. Pantaleo, & E. J. Kremer. (2008) Activation of a dendritic cell-T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells. Journal of Experimental Medicine. DOI: 10.1084/jem.20081786
Stuffed with duck as I am (we don’t do turkey for Thanksgiving in our house) I’m not up to a long post, but I thought a paper in the latest issue of Science was pretty cool. The paper is
Czechowicz, A., Kraft, D., Weissman, I. L., and Bhattacharya, D. (2007). Efficient Transplantation via Antibody-Based Clearance ... Read more »
A Czechowicz, D Kraft, I Weissman, & D Bhattacharya. (2007) Efficient Transplantation via Antibody-Based Clearance of Hematopoietic Stem Cell Niches. Science, 1296-1299. DOI: 10.1126/science.1149726
My last post talked about various species that have limited MHC diversity in their population. I got carried away and forgot to mention the paper that actually prompted that long ramble.
Axolotls are a fairly popular laboratory animal; they are salamanders, famous for their ability to regenerate limbs and for neotony — at ... Read more »
A Richman, G Herrera, V H Reynoso, G Méndez, & L Zambrano. (2007) Evidence for balancing selection at the DAB locus in the axolotl, Ambystoma mexicanum. International Journal of Immunogenetics, 34(6), 475-478. DOI: 10.1111/j.1744-313X.2007.00721.x
Oncolytic VSV (gold) infecting lung tumors1
Oncolytic viruses are a concept I’d like to be more excited by than I am.2 It’s an idea that seemed really exciting when I first came across it, but the more I thought about it the more dubious I was. But a recent paper helps me feel better about at ... Read more »
Jian Qiao, Timothy Kottke, Candice Willmon, Feorillo Galivo, Phonphimon Wongthida, Rosa Diaz, Jill Thompson, Pamela Ryno, Glen Barber, John Chester.... (2007) Purging metastases in lymphoid organs using a combination of antigen-nonspecific adoptive T cell therapy, oncolytic virotherapy and immunotherapy. Nature Medicine. DOI: 10.1038/nm1681
The point of a vaccine trial is to test whether the vaccine works. If you get an answer to that question, the trial is a success. The answer may be “No”, in which case the vaccine is a failure, but the trial would still be a success. (The STEP HIV vaccine trial was therefore a [...]... Read more »
Ogutu, B., Apollo, O., McKinney, D., Okoth, W., Siangla, J., Dubovsky, F., Tucker, K., Waitumbi, J., Diggs, C., Wittes, J.... (2009) Blood Stage Malaria Vaccine Eliciting High Antigen-Specific Antibody Concentrations Confers No Protection to Young Children in Western Kenya. PLoS ONE, 4(3). DOI: 10.1371/journal.pone.0004708
Anti-vaccine loons often claim that the only reason for vaccinations is the capitalist system and the ill-gotten profits of vaccination.
Here’s data1 from that notorious hotbed of capitalism, the People’s Republic of China of 1965, when measles vaccination was introduced. For Shanghai …
The incidence of morbidity associated with measles ranged from 909 to 3,510/100,000 persons during [...]... Read more »
I know all my regular readers1 are expecting me to talk about the bombshell announcements that NK cells have memory, but I’ll put that off for a bit and instead quickly note a very cool advance on a story I’ve mentioned a few times before.
Interferons are among the most critical early warning and protective cytokines, [...]... Read more »
D. Basu, M. P. Walkiewicz, M. Frieman, R. S. Baric, D. T. Auble, & D. A. Engel. (2008) Novel Influenza Virus NS1 Antagonists Block Replication and Restore Innate Immune Function. Journal of Virology, 83(4), 1881-1891. DOI: 10.1128/JVI.01805-08
CTL (green) and HSV-infected cells (red)
(from Akiko Iwasaki)
Last time I talked about herpesvirus immune evasion of cytotoxic T lymphocytes, I cautiously wondered if there might be a theme emerging: Do these genes mainly help the virus with latent infection?
Immune evasion of CTL seems to be pretty much universal among the millions of different herpesvirus species ... Read more »
Linda Wakim, Claerwen M Jones, Thomas Gebhardt, Christopher M Preston, & Francis R Carbone. (2008) CD8 T-cell attenuation of cutaneous herpes simplex virus infection reduces the average viral copy number of the ensuing latent infection. Immunology and Cell Biology. DOI: 10.1038/icb.2008.47
TcR interacting with artificial membrane1
Earlier this week I talked about the phenomenon of viruses that downregulate MHC class II. The “purpose” of this blockade is kind of unclear to me, because the immunity driven by MHC class II is not focused on the cell it’s attached to, but rather spills out broadly over a ... Read more »
B Sullivan, & L Coscoy. (2007) Downregulation of the T-Cell Receptor Complex and Impairment of T-Cell Activation by Human Herpesvirus 6 U24 Protein. Journal of Virology, 82(2), 602-608. DOI: 10.1128/JVI.01571-07
HIV infecting a macrophage1
It’s never been very clear to me why a virus would want to invest in blocking MHC class II. Since there are viruses that apparently do invest this way2 I may be missing something about virus-host interactions.
MHC class II is certainly critical to the immune response. People without MHC class II, as ... Read more »
A Hussain, C Wesley, M Khalid, A Chaudhry, & S Jameel. (2007) Human Immunodeficiency Virus Type 1 Vpu Protein Interacts with CD74 and Modulates Major Histocompatibility Complex Class II Presentation. Journal of Virology, 82(2), 893-902. DOI: 10.1128/JVI.01373-07
The recent papers on TRIM5-cyclophilin fusion proteins as retroviral restriction systems,1 and my nattering about myxomavirus the other day, reminded me of another paper I recently read.
TRIM5 is one of a family of proteins that prevent replication of certain retroviruses; the TRIM5-CYP fusion protein protects against infection so that, for example, feline immunodeficiency virus doesn’t ... Read more »
Timothy Sheahan, Barry Rockx, Eric Donaldson, Amy Sims, Raymond Pickles, Davide Corti, & Ralph Baric. (2008) Mechanisms of zoonotic severe acute respiratory syndrome coronavirus host range expansion in human airway epithelium. Journal of virology, 82(5).
Igor Jurak, & Wolfram Brune. (2006) Induction of apoptosis limits cytomegalovirus cross-species infection. The EMBO Journal, 25(11), 2634-2642. DOI: 10.1038/sj.emboj.7601133
Wenhui Li, Chengsheng Zhang, Jianhua Sui, Jens H Kuhn, Michael J Moore, Shiwen Luo, Swee-Kee Wong, I-Chueh Huang, Keming Xu, Natalya Vasilieva.... (2005) Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. The EMBO journal, 24(8).
Metchnikov: “Lecons sur la pathologie” (1892)
There are times when you just feel like the universe is out to get you. For example, we know that inflammation can drive tumor formation; but a paper just came out that suggests reducing inflammation can also drive tumor formation. 1 It doesn’t seem fair.
I’ve previously mentioned the [...]... Read more »
Granville, C., Memmott, R., Balogh, A., Mariotti, J., Kawabata, S., Han, W., LoPiccolo, J., Foley, J., Liewehr, D., Steinberg, S.... (2009) A Central Role for Foxp3 Regulatory T Cells in K-Ras-Driven Lung Tumorigenesis. PLoS ONE, 4(3). DOI: 10.1371/journal.pone.0005061
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