Journal Club Sep 12/13 & Sep 26/27


Journal club presentations will presented by groups of two students. Each pair should pick and read a paper from this list and give a 15 minute presentation on the paper in class. Your main goal is to explain the important parts of the paper to your audience.
In the presentation the following points should be covered:

  1. A short summary of background information on the topic.
  2. The major question the paper is addressing.
  3. A summary of the major experiments and results (explain the relevant techniques).
  4. A short summary of the major conclusions drawn.


You should make your presentation understandable to your audience, who have not read the paper. You don't have to explain every little detail of the paper (that would take longer than 15 minutes!), but you should cover all important points. Make everything as clear as possible. Overheads or powerpoint presentations should be used.



You may choose one of the following papers to present:

List of Journal Club papers:

Link to PubMed (A search site for Scientific Journal Articles)

PubMed Guide


Week 3

DNA deamination mediates innate immunity to retroviral infection. Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, Neuberger MS, Malim MH. Cell. 2003 Jun 13;113(6):803-9.

Abstract: CEM15/APOBEC3G is a cellular protein required for resistance to infection by virion infectivity factor (Vif)-deficient human immunodeficiency virus (HIV). Here, using a murine leukemia virus (MLV)-based system, we provide evidence that CEM15/APOBEC3G is a DNA deaminase that is incorporated into virions during viral production and subsequently triggers massive deamination of deoxycytidine to deoxyuridine within the retroviral minus (first)-strand cDNA, thus providing a probable trigger for viral destruction. Furthermore, HIV Vif can protect MLV from this CEM15/APOBEC3G-dependent restriction. These findings imply that targeted DNA deamination is a major strategy of innate immunity to retroviruses and likely also contributes to the sequence variation observed in many viruses (including HIV).

Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex.  Yu X, Yu Y, Liu B, Luo K, Kong W, Mao P, Yu XF. Science. 2003 Nov 7;302(5647):1056-60.

Abstract:   Human immunodeficiency virus-1 (HIV-1) Vif is essential for viral evasion of host antiviral factor CEM15/APOBEC3G. We report that Vif interacts with cellular proteins Cul5, elongins B and C, and Rbx1 to form an Skp1-cullin-F-box (SCF)-like complex. The ability of Vif to suppress antiviral activity of APOBEC3G was specifically dependent on Cul5-SCF function, allowing Vif to interact with APOBEC3G and induce its ubiquitination and degradation. A Vif mutant that interacted with APOBEC3G but not with Cul5-SCF was functionally inactive. The Cul5-SCF was also required for Vif function in distantly related simian immunodeficiency virus mac. These results indicate that the conserved Cul5-SCF pathway used by Vif is a potential target for antiviral development.

Week 5

A membrane protein required for dislocation of misfolded proteins from the ER.

Lilley BN, Ploegh HL. Nature. 2004 Jun 24;429(6994):834-40.

Abstract: After insertion into the endoplasmic reticulum (ER), proteins that fail to fold there are destroyed. Through a process termed dislocation such misfolded proteins arrive in the cytosol, where ubiquitination, deglycosylation and finally proteasomal proteolysis dispense with the unwanted polypeptides. The machinery involved in the extraction of misfolded proteins from the ER is poorly defined. The human cytomegalovirus-encoded glycoproteins US2 and US11 catalyse the dislocation of class I major histocompatibility complex (MHC) products, resulting in their rapid degradation. Here we show that US11 uses its transmembrane domain to recruit class I MHC products to a human homologue of yeast Der1p, a protein essential for the degradation of a subset of misfolded ER proteins. We show that this protein, Derlin-1, is essential for the degradation of class I MHC molecules catalysed by US11, but not by US2. We conclude that Derlin-1 is an important factor for the extraction of certain aberrantly folded proteins from the mammalian ER.

The ER-luminal domain of the HCMV glycoprotein US6 inhibits peptide translocation by TAP. Ahn K, Gruhler A, Galocha B, Jones TR, Wiertz EJ, Ploegh HL, Peterson PA, Yang Y, Fruh K. Immunity. 1997 May;6(5):613-21.

Abstract: Human cytomegalovirus (HCMV) inhibits MHC class I antigen presentation by a sequential multistep process involving a family of unique short (US) region-encoded glycoproteins. US3 retains class I molecules, whereas US2 and US11 mediate the cytosolic degradation of heavy chains by the proteosomes. In US6-transfected cells, however, intracellular transport of class I molecules is impaired because of defective peptide translocation by transporters associated with antigen processing (TAP). Peptide transport is restored in HCMV mutants lacking US6. In contrast to the cytosolic herpes simplex virus protein ICP47, US6 interacts with TAP inside the endoplasmic reticulum lumen, as shown by US6 derivatives lacking the transmembrane and cytoplasmic domains and by the observation that US6 does not prevent peptides from binding to TAP. Thus, HCMV targets TAP for immune escape by a molecular mechanism different from that of herpes simplex virus.

PMID: 9175839 [PubMed - indexed for MEDLINE]



This web site was created by Tim Melton. Site modified on Aug 2007.