Human Cytomegalovirus Glycoprotein-Initiated Signaling Mediates the Aberrant Activation of Akt

2020/06/03 by Jamil Mahmud, Michael J. Miller, Aaron M. Altman +1 · 3 citations
Medicine · Immunology and Microbiology · #Cytomegalovirus and herpesvirus research #Immune Cell Function and Interaction #Herpesvirus Infections and Treatments

paper · doi:10.1128/jvi.00167-20

Abstract

Human cytomegalovirus (HCMV) infection is endemic throughout the world regardless of socioeconomic conditions and geographic locations with a seroprevalence reaching up to 100% in some developing countries. Although asymptomatic in healthy individuals, HCMV can cause severe multiorgan disease in immunocompromised or immunonaive patients. HCMV disease is a direct consequence of monocyte-mediated systematic spread of the virus following infection. Because monocytes are short-lived cells, HCMV must subvert the natural short life-span of these blood cells by inducing a distinct activation of Akt, a serine/theonine protein kinase. In this work, we demonstrate that HCMV glycoproteins gB and gH work in tandem to reroute classical host cellular receptor signaling to aberrantly activate Akt and drive survival of infected monocytes. Deciphering how HCMV modulates the cellular pathway to induce monocyte survival is important to develop a new class of anti-HCMV drugs that could target and prevent spread of the virus by eliminating infected monocytes.

Citations

• Induction of endogenous human cytomegalovirus gene expression after differentiation of monocytes from healthy carriers
• Human Cytomegalovirus Stimulates Monocyte-to-Macrophage Differentiation via the Temporal Regulation of Caspase 3
• Human Cytomegalovirus Induces Monocyte Differentiation and Migration as a Strategy for Dissemination and Persistence
• Human Cytomegalovirus Stimulates the Synthesis of Select Akt-Dependent Antiapoptotic Proteins during Viral Entry To Promote Survival of Infected Monocytes
• Human Cytomegalovirus Induces an Atypical Activation of Akt To Stimulate the Survival of Short-Lived Monocytes

Cited by

• Human cytomegalovirus modulates mTORC1 to redirect mRNA translation within quiescently infected monocytes
• Human cytomegalovirus-triggered necroptosis is suppressed by sequestration of MLKL in the nucleus of infected monocytes
• Knockout of key receptors (PDGFRA and NRP2) in the guinea pig model blocks direct and endocytic pathways of CMV cell entry

Related

• Human Cytomegalovirus Induces an Atypical Activation of Akt To Stimulate the Survival of Short-Lived Monocytes
• Human Cytomegalovirus Stimulates the Synthesis of Select Akt-Dependent Antiapoptotic Proteins during Viral Entry To Promote Survival of Infected Monocytes
• Human cytomegalovirus-triggered necroptosis is suppressed by sequestration of MLKL in the nucleus of infected monocytes
• Human cytomegalovirus modulates mTORC1 to redirect mRNA translation within quiescently infected monocytes
• Human Cytomegalovirus Induces Monocyte Differentiation and Migration as a Strategy for Dissemination and Persistence