jazyk / language:
INTERAKTÍVNA KONFERENCIA
MLADÝCH VEDCOV
Späť do sekcie

New insight to immunomodulatory potential of human CD160 receptor in cytomegalovirus immune signaling

Diskusná interakcia
Celkové prevedenie (dizajn)
Vedecká práca
Schovať hodnotenia

Prejsť do diskusie

New insight to immunomodulatory potential of human CD160 receptor in cytomegalovirus immune signaling

Simona Lenhartová 1 Ivana Nemčovičová 1 Marek Nemčovič 2

1Virologický ústav, Biomedicínske centrum SAV, Bratislava, Slovensko
2Chemický ústav SAV, Bratislava, Slovensko
simonnalenhartova@gmail.com

Overview

Almost all viruses have developed elaborate, and often complex strategies to circumvent host innate immunity highlighting the importance of the innate immune response. Human cytomegalovirus (HCMV, HHV-5), one of eight human herpesviruses, is the leading viral cause of congenital birth defects and is responsible for morbidity and mortality in immunosuppressed individuals. Currently, an effective vaccine for HCMV has not been licensed, although it has been considered a global health priority. In recent years, several immunoreceptors were identified as candidate target for immunotherapy, however human CD160 was selected from the crowd because its specificity for HCMV. The relationship of CD160 to HVEM (TNFRSF14), and its viral ortholog UL144 (encoded by HCMV or RhCMV) are nowadays being extensively studied because of their specific properties in immune modulation. Answering such questions has the potential to reveal novel mechanisms of immune evasion, new cell surface drug targets resulting in new immunomodulatory biologics and an improved understanding of HCMV biology.

Results and Discussion

CD160 was firstly identified as a co-inhibitory molecule that binds endogenous HVEM with a similar affinity to human checkpoint receptor BTLA [1, 2]. In our study, we focused on biological preparation and characterization of human CD160 and the viral HVEM ortholog UL144 (encoded by Human and Rhesus CMV) expressed and isolated by using the BV-Sf9 suspension expression system. HCMV UL144, the viral mimic of HVEM, does not bind CD160, which is most probably due to altered N-linked or O-linked glycosylation or other posttranslational changes. Mutant of UL144 (GD, glycosylation deficient) lacking several glycosylation sites (N61, N70, N73, N78, N91, N99, N116) was generated and we have determined whether its binding to CD160 was impacted. The study has indicated that GD mutant of UL144 could bind CD160 with similar affinity as observed for soluble HVEM [3]. Additionally, we have performed the crystallization condition screenings for CD160 alone (thrombin digested Fc-fusion part of the protein), HVEM-CD160 and rhUL144-CD160 protein complexes. The preliminary crystallization conditions were found and further optimized. The suitable crystals were tested for X-ray diffraction. Both protein crystals of CD160 and HVEM-CD160 complex were subjected to finely focused monochromatic beam of X-rays, producing a diffraction pattern of regularly spaced spots at resolution of 1.22 Å and 2.24 Å, respectively. The structural data are being optimized and processed for phasing.

This research is supported by the contribution of the Slovak Research and Development Agency (APVV-14-0376) and the contribution of the Scientific Grant Agency of the Slovak Republic (02/0020/18 and 02/0060/21).
1. Kojima R., Kajikawa M., Shiroishi M., Kuroki M., Maenaka. (2011) J. Mol. Biol. 413, 762-772.
2. Šedý R. J., Bjordahl L. R., Bekiaris V., et al. (2013) J. Immunol. 191, p. 828.
3. Lenhartová S., Kempová V., Benko M. (2020) Mater. Struct. 27, p. 20.
Zdá sa, že Váš internetový prehliadač nepodporuje prehliadanie PDF dokumentov.
Pre zobrazenie súboru je potrebné maš nainštalovaný Adobe Reader.

Diskusia

Diskusia je zatiaľ prázdna, buďte prvý komentujúci
Naši partneri
Generálny partner

Partneri
Špeciálne poďakovanie
Mediálni partneri
Inzercia zadarmo
Usporiadateľ