187 research outputs found
Transition of the Baithi Chawl
No full textIn the next three decades, the lanet’s rate of urbanization will increase at a fast rate, adding 2,5 billion new dwellers to the current urban o ulation. To accom¬modate this demogra hic growth, the world needs to tackle the many challenges of sustainable and fair urban develo ment. Right now, urbanization in the Global South ha ens in mainly unsustainable ways, with a roximately 850 million eo ¬le living in slums in 2014 (1/3 of all urban dwellers). Rethinking the current systems of affordable housing roduction is a major challenge that needs urgent actions. The stakeholders involved in housing roduction, in general, and the architectu¬re disci line, in articular, need a critical evaluation of their rocesses, methods and strategies to answer some ressing questions. Where will all these new urban dwellers live? More im ortantly erha s, how will these new urbanites dwell? What will be the role of architects and urban lanners in this rocess? The graduation studio Mixing Mumbai: Affordable Housing for Inclusive Develo ¬ment aims to stimulate the artici ants to contribute answers to these questions, engaging with ressing dwelling and urban issues in develo ing territories, as well as with the increasing cross-cultural character of contem orary architectural rac¬tice.Architecture, Urbanism and Building Sciences | Global Housin
A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates
No full textgamma 1-Herpesviruses such as Epstein-Barr virus (EBV) have a unique ability to amplify virus loads in vivo through latent growth-transforming infection. Whether they, like alpha- and beta-herpesviruses, have been driven to actively evade immune detection of replicative (lytic) infection remains a moot point. We were prompted to readdress this question by recent work (Pudney, V.A., A.M. Leese, A.B. Rickinson, and A.D. Hislop. 2005. J. Exp. Med. 201:349-360; Ressing, M.E., S.E. Keating, D. van Leeuwen, D. Koppers-Lalic, I.Y. Pappworth, E.J.H.J. Wiertz, and M. Rowe. 2005. J. Immunol. 174:6829-6838) showing that, as EBV-infected cells move through the lytic cycle, their susceptibility to EBV-specific CD8(+) T cell recognition falls dramatically, concomitant with a reductions in transporter associated with antigen processing (TAP) function and surface human histocompatibility leukocyte antigen (HLA) class I expression. Screening of genes that are unique to EBV and closely related gamma 1-herpesviruses of Old World primates identified an early EBV lytic cycle gene, BNLF2a, which efficiently blocks antigen-specific CD8(+) T cell recognition through HLA-A-, HLA-B-, and HLA-C-restricting alleles when expressed in target cells in vitro. The small (60-amino acid) BNLF2a protein mediated its effects through interacting with the TAP complex and inhibiting both its peptide- and ATP-binding functions. Furthermore, this targeting of the major histocompatibility complex class I pathway appears to be conserved among the BNLF2a homologues of Old World primate gamma 1-herpesviruses. Thus, even the acquisition of latent cycle genes endowing unique growth-transforming ability has not liberated these agents from evolutionary pressure to evade CD8(+) T cell control over virus replicative foci
A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates
No full textgamma 1-Herpesviruses such as Epstein-Barr virus (EBV) have a unique ability to amplify virus loads in vivo through latent growth-transforming infection. Whether they, like alpha- and beta-herpesviruses, have been driven to actively evade immune detection of replicative (lytic) infection remains a moot point. We were prompted to readdress this question by recent work (Pudney, V.A., A.M. Leese, A.B. Rickinson, and A.D. Hislop. 2005. J. Exp. Med. 201:349-360; Ressing, M.E., S.E. Keating, D. van Leeuwen, D. Koppers-Lalic, I.Y. Pappworth, E.J.H.J. Wiertz, and M. Rowe. 2005. J. Immunol. 174:6829-6838) showing that, as EBV-infected cells move through the lytic cycle, their susceptibility to EBV-specific CD8(+) T cell recognition falls dramatically, concomitant with a reductions in transporter associated with antigen processing (TAP) function and surface human histocompatibility leukocyte antigen (HLA) class I expression. Screening of genes that are unique to EBV and closely related gamma 1-herpesviruses of Old World primates identified an early EBV lytic cycle gene, BNLF2a, which efficiently blocks antigen-specific CD8(+) T cell recognition through HLA-A-, HLA-B-, and HLA-C-restricting alleles when expressed in target cells in vitro. The small (60-amino acid) BNLF2a protein mediated its effects through interacting with the TAP complex and inhibiting both its peptide- and ATP-binding functions. Furthermore, this targeting of the major histocompatibility complex class I pathway appears to be conserved among the BNLF2a homologues of Old World primate gamma 1-herpesviruses. Thus, even the acquisition of latent cycle genes endowing unique growth-transforming ability has not liberated these agents from evolutionary pressure to evade CD8(+) T cell control over virus replicative foci
Evasion of T cell immunity by Epstein-Barr virus
No full textImmune evasion strategies are thought to contribute essentially to the life cycle of persistent viruses by delaying the elimination of the infected cell long enough to enable the virus to replicate. Exemplary in this context are the herpesviruses, large DNA viruses that are carried as a persistent and largely asymptomatic infection by the vast majority of adults. Epstein-Barr virus (EBV), the prototypic gamma-herpesvirus, is the causative agent of infectious mononucleosis and of post-transplant lymphoproliferative disorders and is associated with Burkitt’s lymphoma, nasopharyngeal carcinoma, and Hodgkin’s lymphoma. EBV-specific immune responses are present in infected individuals, yet the virus cannot be cleared. EBV resides in B cells, mostly in a latent state with limited viral gene expression. In contrast, over eighty viral proteins are expressed during the replicative phase that is required for virus production and transmission to other hosts. At this stage,immune evasion strategies are important to avoidelimination of virus-producing cells. This thesis describes the identification and characterization of a new and very powerful EBV-encoded immune evasion protein, the TAP inhibitor BNLF2a. Furthermore, it was investigated how BGLF5, another recently discovered EBV immune evasion protein, blocks host protein synthesis. During productive EBV infection, the immune evasion protein BNLF2a inhibits transport of antigenic peptides into the ER via the Transporter associated with Antigen Processing (TAP). As a consequence, antigen presentation via HLA class I molecules is impaired and T cell recognition is avoided. In virus-producing B cells, the timing of BNLF2a expression allows for immediate interference with the presentation of viral antigens by HLA class I molecules. BNLF2a is highly expressed early upon EBV reactivation and declines during progression of viral replication. BNLF2a displays characteristics of a tail-anchored (TA) protein: we find the viral protein to be inserted into membranes post-translationally, with its hydrophobic C-terminal domain functioning as a membrane anchor. This topology leaves BNLF2a’s N-terminal domain exposed in the cytosol, where it inhibits TAP function. Expression of the EBV lytic phase protein BGLF5 results in a general block in the synthesis of cellular proteins, including HLA class I molecules. This host shutoff activity of BGLF5 relies on its ability to induce degradation of mRNA. Originally, BGLF5 was identified as a DNase, being involved in viral replication. More recently, BGLF5 was demonstrated to have RNase activity as well. When analysing various mutants of BGLF5, we found, on the one hand, that a point mutation destroying DNase function also blocked RNase activity, implying both nuclease activities to share a catalytic site. On the other hand, other mutations were more selective affecting either DNA degradation or host shutoff, pointing towards separation of these two functions. In conclusion, the EBV lytic phase proteins BNLF2a and BGLF5 contribute to the obstruction of HLA class I-restricted antigen presentation to cytotoxic T cells. Interference with T cell recognition during productive EBV infection is anticipated to create a window for the generation of viral progeny in the face of memory T cell immunity
Varicellovirus UL 49.5 proteins differentially affect the function of the transporter associated with antigen processing, TAP
No full textCytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms
Individual data metaanalysis of case control studies with differing case entities, applied to the genetic assocation between a Tp53 SN-polymorphism and neoplasms of cervix uteri
No full text
- …
