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Home > Research > Virology > Audrey ESCLATINE: Virulence and Latency of herpes Viruses

Audrey ESCLATINE : Group Presentation

Our objective is to analyse the relationships between viruses of Herpesviridae family, such as Herpes simplex virus HSV-1 and Human cytomegalovirus, at both the replicative cycle and the latent infection and their hosts, by in vitro and in vivo approaches, with an original latency model.

Project

The main objective of our team is to study Human Herpesviruses and to focus on virus-host interactions. We have a particular interest on the cellular defense mechanisms against pathogens, on the regulation of viral latency and on the hijacking by viruses of the cellular machinery of transport. We are studying several different Herpesvirus, such as Herpes Simplex Virus type 1 (HSV-1), human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV).

1. We are notably focusing on autophagy, a biological process which leads to degradation of cytosolic components by the lysosome. Beyond its functions in cell maintenance, it appears now that autophagy is critical in establishing and regulating immune responses against pathogens, with potential antiviral properties. We have established that both HSV-1 and HCMV are able to negatively modulate the formation of autophagosomes, the double membrane vesicles characteristic of autophagy. We have identified several gene products of HSV-1 and HCMV involved in this modulation and their mechanisms of action (Figure 1). We are now deciphering the consequences of autophagy manipulation by these viruses, notably on innate and adaptative immunity and virulence.

Figure 1}

: Quantification of GFP-LC3 dots by Cellomics ArrayScan in HeLa cells. Number of autophagosomes (green spots) is clearly decreased after expression of the HCMV protein, IRS1 (red staining).

Latency is found in all viruses of the Herpesviridae family, allows them to persist indefinitely in their host and is characterized by the presence of viral genome as an episome in the nucleus. Regarding HSV-1, this state is also characterized by the accumulation of Latency Associated Transcripts (LATs). Concerning latency, we characterized a mouse model mimicking the natural history of HSV 1 infection in human (Figure 2), which allows us to study latency as well as reactivation in different neurological sites. We use this model to elucidate the role of non-coding RNAs, the LATs during latency, in combination with in vitro experiments to join in vivo aspects and more fundamentals insights. This in vivo mouse model is also used to test innovative therapeutic approaches against HSV-1 infections.

Figure 2: Oro ocular model of HSV-1 infection. Non coding RNA LATs accumulate especially in the trigeminal ganglion (TG).

Viral dissemination within the host requires efficient, fact and directed transport of viral particles. This is particularly important for neurotropic viruses such as HSV-1, which have to travel through large distances. Using fluorescent viruses, live-cell imaging technology and molecular biology, we aim at understanding the virus-host interactions involved in viral transport (Figure 3).

Figure 3: HSV-1 capsids travelling within a neuron

Keywords :

Virus, HSV-1, HCMV, EBV, Latency, LATs, transport, centrosome, autophagy, host defense

Contact :


ESCLATINE Audrey [Professor - UPSud]
Virulence and Latency of Herpes viruses [Leader]
+331 4683 5292 Fac. Pharma - Chatenay

published on , updated on