Herpes simplex virus infections of cortical brain cells: the proteome and secretome of the host

ABSTRACT: Herpes simplex virus-1 (HSV-1) infections of the brain cause a severe neuroinflammatory condition – Herpes simplex encephalitis (HSE). During the acute phase, HSV-1 changes the host cells to facilitate its own replication and to escape host immunity. However, the host reacts with a severe neuroinflammation which may be beneficial for viral clearance or detrimental inducing neuronal damage and hindering regeneration. Indeed, surviving HSE-patients often suffer from an incomplete regeneration with memory deficits and other neuropsychiatric symptoms. HSV-1 infects different cell types such as neurons, astrocytes, and oligodendrocytes all of which participate in the host response. This includes a changed paracrine signaling. However, the host response has not been characterized on a global molecular level so far. Here, we infected primary mixed cortical cells with HSV-1 and analyzed the proteome and the secretome of the host. We identified 28 differentially regulated proteins in the host proteome involved in endocytosis, vesicle trafficking at the golgi-apparatus, and inflammasome formation. In the secretome, we identified 71 differentially regulated proteins with a subset involved in axonal regeneration. Endocytosis and vesicle trafficking are critical for viral entry and envelopment. The suppression of inflammasome activity is crucial for viral spread. Thus, our proteomic analysis hints for potential molecules regulating viral production and spread in brain cells. Moreover, the secretome analysis gives rise to a set of proteins involved in neuroregeneration.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Nerve Cord, Macrophage

SUBMITTER: Andreas Picjh  

LAB HEAD: Andreas Pich

PROVIDER: PXD018819 | Pride | 2021-09-09

REPOSITORIES: Pride