Recombinant viruses as tools to study human cytomegalovirus immune modulation

Besold, Katrin; Plachter, Bodo

doi:10.1007/s00430-008-0083-4

Cited by 9 publications

(8 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, we identified a number of individual effects of HCMV evasins on T cell recognition through particular MHC allotypes that would not have been predicted from previous studies, as we now discuss in more detail. US2 and US11 mediate reimport of MHC I H chains into the cytosol and proteasomal degradation (17)(18)(19)47) by interacting with the a2, a3 and cytoplasmic regions of the MHC I H chain (27,35,48). For US2, contacts with amino acids at the intersection of the a2 and a3 domains of the MHC I H chain appear to be of particular importance (27,49).…”

Section: Discussionmentioning

confidence: 99%

CD8 T Cell–Evasive Functions of Human Cytomegalovirus Display Pervasive MHC Allele Specificity, Complementarity, and Cooperativity

Ameres

Besold

Plachter

et al. 2014

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Immunoevasive proteins (“evasins”) of human CMV (HCMV) modulate stability and localization of MHC class I (MHC I) molecules, and their supply of antigenic peptides. However, it is largely unknown to what extent these evasins interfere with recognition by virus-specific CD8 T cells. We analyzed the recognition of HCMV-infected cells by a panel of CD8 T cells restricted through one of nine different MHC I allotypes. We employed a set of HCMV mutants deleted for three or all four of the MHC I modulatory genes US2, US3, US6, and US11. We found that different HCMV evasins exhibited different allotype-specific patterns of interference with CD8 T cell recognition of infected cells. In contrast, recognition of different epitopes presented by the same given MHC I allotype was uniformly reduced. For some allotypes, single evasins largely abolished T cell recognition; for others, a concerted action of evasins was required to abrogate recognition. In infected cells whose Ag presentation efficiency had been enhanced by IFN-γ pretreatment, HCMV evasins cooperatively impared T cell recognition for several different MHC I allotypes. T cell recognition and MHC I surface expression under influence of evasins were only partially congruent, underscoring the necessity to probe HCMV immunomodulation using specific T cells. We conclude that the CD8 T cell evasins of HCMV display MHC I allotype specificity, complementarity, and cooperativity.

show abstract

Section: Discussionmentioning

confidence: 99%

CD8 T Cell–Evasive Functions of Human Cytomegalovirus Display Pervasive MHC Allele Specificity, Complementarity, and Cooperativity

Ameres

Besold

Plachter

et al. 2014

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…At this time, structural proteins, such as pp65, delivered with virus particles feed rapidly into the MHC I presentation pathway (Besold & Plachter, 2008;McLaughlin-Taylor et al, 1994). The same may be true for other structural proteins that are prominent targets of CD8 + T-cell memory responses (Boppana & Britt, 1996;Elkington et al, 2003;Sylwester et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Peptides from IE1, for example, are already presented to CD8 + T-cells at 6 h p.i. (Besold & Plachter, 2008), but may become visible even earlier with IE peptides with higher MHC I affinity. This is a dilemma for the virus, as IE proteins are essential for the initiation of lytic infection, but may mediate killing by CTLs when presented by MHC I. Interestingly, however, infection with a US2-11-competent virus completely abrogated IE1 TMY presentation from 1 to 96 h p.i.…”

Section: Discussionmentioning

confidence: 99%

“…This is a dilemma for the virus, as IE proteins are essential for the initiation of lytic infection, but may mediate killing by CTLs when presented by MHC I. Interestingly, however, infection with a US2-11-competent virus completely abrogated IE1 TMY presentation from 1 to 96 h p.i. (Besold & Plachter, 2008). Here we show that immunoevasion is similarly efficient under stringent IE conditions: presentation of different IE1 epitopes is suppressed strongly after infection with US2-11-competent strains, but not after infection with US2-11-deleted virus (Figs 2a, 5a, b).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Suppression of CD8+ T-cell recognition in the immediate-early phase of human cytomegalovirus infection

Hesse

Ameres

Besold

et al. 2013

Journal of General Virology

Self Cite

View full text Add to dashboard Cite

Human cytomegalovirus (HCMV) interferes with MHC class I-restricted antigen presentation and thereby reduces recognition by CD8 + T-cells. This interference is mediated primarily by endoplasmic reticulum-resident glycoproteins that are encoded in the US2-11 region of the viral genome. Such a suppression of recognition would be of particular importance immediately after infection, because several immunodominant viral antigens are already present in the cell in this phase. However, which of the evasion proteins gpUS2-11 interfere(s) with antigen presentation to CD8 + T-cells at this time of infection is not known. Here we address this question, using recombinant viruses (RV) that express only one of the immunoevasins gpUS2, gpUS3 or gpUS11. Infection with RV-US3 had only a limited impact on the presentation of peptides from the CD8 + T-cell antigens IE1 and pp65 under immediate-early (IE) conditions imposed by cycloheximide/ actinomycin D blocking. Unexpectedly, both RV-US2 and RV-US11 considerably impaired the recognition of IE1 and pp65 by CD8 + T-cells, and both US2 and, to a lesser extent, US11 were transcribed under IE conditions. Thus, gpUS2 and gpUS11 are key effectors of MHC class I immunoevasion immediately after HCMV infection.

show abstract

“…These cytoplasmic accumulations reached sizes up to 5 m. It remains unclear, whether they are related to DB. In contrast to cells infected with RV-HB5 and RV-EP0, cells infected with the other recombinant viruses did not display any formation of DB, although some large electron-dense structures without any speciWc organisation were observed in the cytoplasm of RV-EP1 and RV-VR1 infected cells ImmunoXuorescence analyses were carried out as described in the accompanying article [51]. White bars represent 10 m. c Immunoblot analysis of the amount of fusion protein packaged in the extracellular NIEPs fractions, collected by glyceroltartrate gradient centrifugation [43].…”

Section: Ultrastructural Analysis Of Infected Cellsmentioning

confidence: 99%

Refinement of strategies for the development of a human cytomegalovirus dense body vaccine

Mersseman

Böhm

Holtappels

et al. 2008

Med Microbiol Immunol

Self Cite

View full text Add to dashboard Cite

Development of a vaccine against human cytomegalovirus (HCMV) infection has been identiWed as a high priority goal in biomedical research, yet no vaccine has been licensed until now. Recombinant subviral dense bodies (recDB) are a promising basis for the establishment of such a vaccine. In this article, strategies for the generation of recDB, based on recombination-mediated genetic engineering of the 230 kb HCMV DNA genome in E. coli are outlined. Analysis of viral mutants that were constructed in this process provided the proof-of-principle that heterologous antigens can be packaged into recDB and that these particles prime CD8 T cell responses against the recombinant antigen upon their application to HLA-A2 transgenic mice.

show abstract

Recombinant viruses as tools to study human cytomegalovirus immune modulation

Cited by 9 publications

References 35 publications

CD8 T Cell–Evasive Functions of Human Cytomegalovirus Display Pervasive MHC Allele Specificity, Complementarity, and Cooperativity

CD8 T Cell–Evasive Functions of Human Cytomegalovirus Display Pervasive MHC Allele Specificity, Complementarity, and Cooperativity

Suppression of CD8+ T-cell recognition in the immediate-early phase of human cytomegalovirus infection

Refinement of strategies for the development of a human cytomegalovirus dense body vaccine

Contact Info

Product

Resources

About