TY  - JOUR
A1  - Koster, Stefanie
A1  - Gurumurthy, Rajendra Kumar
A1  - Kumar, Naveen
A1  - Prakash, Pon Ganish
A1  - Dhanraj, Jayabhuvaneshwari
A1  - Bayer, Sofia
A1  - Berger, Hilmar
A1  - Kurian, Shilpa Mary
A1  - Drabkina, Marina
A1  - Mollenkopf, Hans-Joachim
A1  - Goosmann, Christian
A1  - Brinkmann, Volker
A1  - Nagel, Zachary
A1  - Mangler, Mandy
A1  - Meyer, Thomas F.
A1  - Chumduri, Cindrilla
T1  - Modelling Chlamydia and HPV co-infection in patient-derived ectocervix organoids reveals distinct cellular reprogramming
JF  - Nature Communications
N2  - Coinfections with pathogenic microbes continually confront cervical mucosa, yet their implications in pathogenesis remain unclear. Lack of in-vitro models recapitulating cervical epithelium has been a bottleneck to study coinfections. Using patient-derived ectocervical organoids, we systematically modeled individual and coinfection dynamics of Human papillomavirus (HPV)16 E6E7 and Chlamydia, associated with carcinogenesis. The ectocervical stem cells were genetically manipulated to introduce E6E7 oncogenes to mimic HPV16 integration. Organoids from these stem cells develop the characteristics of precancerous lesions while retaining the self-renewal capacity and organize into mature stratified epithelium similar to healthy organoids. HPV16 E6E7 interferes with Chlamydia development and induces persistence. Unique transcriptional and post-translational responses induced by Chlamydia and HPV lead to distinct reprogramming of host cell processes. Strikingly, Chlamydia impedes HPV-induced mechanisms that maintain cellular and genome integrity, including mismatch repair in the stem cells. Together, our study employing organoids demonstrates the hazard of multiple infections and the unique cellular microenvironment they create, potentially contributing to neoplastic progression.
KW  - Chlamydia
KW  - HPV
KW  - cellular reprogramming
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301349
VL  - 13
IS  - 1
ER  - 
TY  - JOUR
A1  - Singh, Krishna P.
A1  - Verma, Neeraj
A1  - Akhoon, Bashir A .
A1  - Bhatt, Vishal
A1  - Gupta, Shishir K.
A1  - Gupta, Shailendra K.
A1  - Smita, Suchi
T1  - Sequence-based approach for rapid identification of cross-clade CD8+ T-cell vaccine candidates from all high-risk HPV strains
JF  - 3 Biotech
N2  - Human papilloma virus (HPV) is the primary etiological agent responsible for cervical cancer in women. Although in total 16 high-risk HPV strains have been identified so far. Currently available commercial vaccines are designed by targeting mainly HPV16 and HPV18 viral strains as these are the most common strains associated with cervical cancer. Because of the high level of antigenic specificity of HPV capsid antigens, the currently available vaccines are not suitable to provide cross-protection from all other high-risk HPV strains. Due to increasing reports of cervical cancer cases from other HPV high-risk strains other than HPV16 and 18, it is crucial to design vaccine that generate reasonable CD8+ T-cell responses for possibly all the high-risk strains. With this aim, we have developed a computational workflow to identify conserved cross-clade CD8+ T-cell HPV vaccine candidates by considering E1, E2, E6 and E7 proteins from all the high-risk HPV strains. We have identified a set of 14 immunogenic conserved peptide fragments that are supposed to provide protection against infection from any of the high-risk HPV strains across globe.
KW  - HPV
KW  - Epitope
KW  - Cytotoxic
KW  - T lymphocytes
KW  - Cervical cancer
KW  - Vaccine
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191056
VL  - 6
ER  -