New study reveals how viruses manipulate intercellular communication and spread infection within tissue using a novel approach to study the viral microenvironment during human cytomegalovirus infection. The findings show differential regulation of host proteins in infected, neighboring, and distal cells, highlighting the importance of intercellular communication in the spread of viral infections. The study also suggests viral manipulation of uninfected neighboring cells as an opportunity to accelerate subsequent rounds of infection. These insights provide a deeper understanding of the molecular mechanisms involved in host-virus interactions.
How viruses manipulate intercellular communication during infection
Cell-to-cell communication plays a crucial role in the functioning of multicellular organisms, as well as in the development of diseases and response to environmental stimuli. However, how viruses manipulate intercellular communication and spread infection within tissue is not well understood.
To address this issue, researchers have developed a new approach to study the viral microenvironment (VME) during human cytomegalovirus (HCMV) infection. They used a lipid-permeable fluorescent protein labeling strategy to differentiate between infected, neighboring, and distal cell populations within the VME. The proteomes of infected, neighboring, distal, and mock cells were then analyzed using quantitative mass spectrometry.
Study reveals how HCMV infection affects host proteins and intercellular communication, increasing susceptibility to subsequent viral infections
The study found that HCMV infection caused differential regulation of host proteins in infected, neighboring, and distal cells. Specifically, infected cells showed up-regulation of proteins related to viral genome replication, viral gene expression, RNA transport, and translation, as well as metabolic rewiring effects and membrane contact site proteins. Neighboring cells showed changes in proteins related to the organization of the cytoskeleton and extracellular matrix, and increased expression of membrane contact site proteins, similar to infected cells. The changes observed in neighboring cells increased their susceptibility to subsequent viral infections, highlighting the importance of intercellular communication in the spread of viral infections.
The researchers also found that HCMV-infected cells affect the cell cycle of neighboring cells, accelerating their progression through the cell cycle and leading to M-phase arrest. This is supported by changes in cellular protein abundances related to the modulation of the cell cycle and flow cytometry-based assays. The study suggests that viral manipulation of uninfected neighboring cells represents an opportunity to overcome a rate-limiting step in chromatin remodeling that leads to the expression of host S phase proteins and thus hasten subsequent rounds of infection.
Molecular mechanisms involved in viral infections and intercellular communication within a VME during human cytomegalovirus infection
Overall, this study provides new insights into the molecular mechanisms involved in viral infections and intercellular communication. The approach used in this study can be applied to investigate other viral infections and further understand the mechanisms involved in host-virus interactions.
Together, our study brings to light the molecular complexities governing inter- and intracellular communication within a VME. Our findings form the foundation for how a virus infection reorganizes the surrounding cellular environment in a proximity-dependent manner. The result of this intracellular signaling is the concurrent virus-directed spread of an infection and host engagement of community-level defenses.