HEИндивидуална стипендия2022–2024

G4-KuRE · Roles of G-quadruplexes in Kaposi’s sarcoma-associated herpesvirus latent REplication

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2022-06-01 → 2024-05-31
Финансиране от ЕС: 188 590 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Специфични ДНК структури в герпесвируса на Капоши се анализират, за да се открият начини за блокиране на неговото размножаване. Това е важно, защото инфекцията с този вирус повишава риска от развитие на рак, особено при хора с отслабен имунитет.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Roles of G-quadruplexes in Kaposi’s sarcoma-associated herpesvirus latent REplication

Herpesviruses have the ability of maintaining themselves in a life-long state of latency after infecting an individual. Some of these viruses, including Kaposi’s sarcoma-associated herpesvirus (KSHV) also behave as oncogenic viruses, as their latent infection constitutes a risk to develop cancer, particularly for immunocompromised individuals. This represents a considerable social and economic burden for low-income countries, but also 2-5% of cancer incidences in Europe can be attributed to oncogenic viruses. Current strategies aim at defining cures for the cancers derived from oncogenic virus infections. A possibly more effective approach would be, however, to identify efficient ways to block the virus from replicating in the infected cells. To tackle this problem the G4-KuRE project achieved two main goals. First, with a novel approach using protein extracts coming from frog eggs, it identified specific DNA structures in the genome of KSHV that are susceptible to being targeted to block viral replication. Second, it identified drugs that can further stabilise those structures and eukaryotic proteins that contribute to their efficient replication. These results constitute a very solid base for the further development of an effective antiviral strategy against KSHV.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Kaposis sarcoma-associated herpesvirus (KSHV) is a widespread oncogenic virus, whose infection can cause Kaposis sarcoma, an incurable cancer frequent in immunocompromised individuals. Similar to other herpesviruses, KSHV establishes a latent infection in the host, characterized by lifelong persistence of the viral genome. Necessary and sufficient for latent infection are the virally expressed latency-associated nuclear antigen (LANA) and highly repetitive GC-rich sequences on the viral genome, named terminal repeats (TRs). While several studies have uncovered the importance of LANA in promoting KSHV DNA replication and segregation during latency, the essential role of the TRs remains poorly understood. In particular, the GC-rich regions contained in the TRs have been speculated to fold into G-quadruplexes (G4), secondary DNA structures that can function as replication barriers, but their roles remain elusive. A deep mechanistic understanding of the ways KSHV maintains itself in latency would be crucial to uncover a way to eradicate the virus from the infected cells, before the onset of Kaposis sarcoma, but this knowledge is missing, mainly due to the methodological limitations of investigating KSHV latent replication solely in cells. With this proposal, in aim to take advantage of the Xenopus laevis egg extract in vitro system to go beyond such limitations and to gain mechanistic insight in the role of G4s in the latency of KSHV. By combining my extensive expertise in the field of DNA replication with the deep knowledge of Prof. Sara Richter at the University of Padua in secondary DNA structures in viral genomes, I aim at mechanistically defining the strategies adopted by KSHV to maintain itself in latency and at identifying approaches to prevent viral maintenance in KSHV infected cells. The proposed project will have great societal impact on cancer prevention, and it will be pivotal for my scientific and personal growth into an independent junior group leader.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITA DEGLI STUDI DI PADOVA · PadovaКоординаторИталия