Biology subjects

Shnayder, M.

Publications and source records attributed to Shnayder, M..

2 recordsLinked to original sources

bioRxiv2022

The molecular principles governing HCMV infection outcome

Infection with Human cytomegalovirus (HCMV) can result in either productive or non-productive infection, the latter potentially leading to establishment of latency, but the molecular factors that dictate these different infection outcomes are elusive. Macrophages are known targets of HCMV and considered to be permissive for productive infection, while monocytes, their precursors, are latently infected. Here we reveal that infection of macrophages is more complex than previously appreciated and can result in either productive or non-productive infection. By analyzing the progression of HCMV infection in monocytes and macrophages using single cell transcriptomics, we uncover that the level of viral gene expression, and specifically the expression of the major immediate early proteins, IE1 and IE2, is the principal barrier for establishing productive infection. On the cellular side, we reveal that the cell intrinsic levels of interferon stimulated genes (ISG), but not their induction, is a main determinant of infection outcome and that intrinsic ISG levels are downregulated with monocyte differentiation, partially explaining why macrophages are more susceptible to productive HCMV infection. We further show that, compared to monocytes, non-productive macrophages maintain higher levels of viral transcripts and are able to reactivate, raising the possibility that they may serve as latency reservoirs. Overall, by harnessing the tractable system of monocyte differentiation we decipher underlying principles that control HCMV infection outcome, and propose macrophages as a potential HCMV reservoir in tissues.

microbiology↗

bioRxiv2017

Defining the Transcriptional Landscape during Cytomegalovirus Latency with Single-Cell RNA Sequencing

Primary infection with human cytomegalovirus (HCMV) results in a lifelong infection due to its ability to establish latent infection, one characterized viral reservoir being hematopoietic cells. Although reactivation from latency causes serious disease in immunocompromised individuals, our molecular understanding of latency is limited. Here, we delineate viral gene expression during natural HCMV persistent infection by analyzing the massive RNA-seq atlas generated by the Genotype-Tissue Expression (GTEx) project. This systematic analysis reveals that HCMV persistence in-vivo is prevalent in diverse tissues. Unexpectedly, we find only viral transcripts that resemble gene expression during stages of lytic infection with no evidence of any highly restricted latency-associated viral gene expression program. To further define the transcriptional landscape during HCMV latent infection, we also used single cell RNA-seq and a tractable experimental latency model. In contrast to current views on latency, we also find no evidence for a specific restricted latency-associated viral gene expression program. Instead, we reveal that latency-associated gene expression largely mirrors a late lytic viral program albeit at much lower levels of expression. Overall, our work has the potential to revolutionize our understanding of HCMV persistence and suggests that latency is governed mainly by quantitative changes, with a limited number of qualitative changes, in viral gene expression.

microbiology↗