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Hosseinzadeh, S.

Publications and source records attributed to Hosseinzadeh, S..

3 recordsLinked to original sources

Viral and bacterial plant pathogens suppress antiviral defense against flaviviruses in their insect vectors

A positive, single-stranded RNA virus member within the Flavivirus genus was identified and characterized infecting Myzus persicae. This new insect-specific virus (ISV), Myzus persicae flavivirus (MpFV), is 23,236 nucleotides in length and encodes a large polyprotein from a single open reading frame. Analysis of conserved domains showed that helicases, NS3-proteases, Fts-J methyltransferase, and an RNA-dependent RNA polymerase are present in the coded polyprotein. Aphid-infecting ISVs have been reported to interact with plant viruses within the vector, modulating its titer and manipulating aphid behavior and morphology. Small RNA (sRNA) profile analysis of the M. persicae sRNA profile demonstrated that the circulative plant virus, potato leafroll virus (PLRV), modified the aphid antiviral immunity against MpFV. Abundant sRNA reads matching MpFV were detected when aphids were fed on healthy plants, sucrose diet, and potato virus Y-infected plants. In contrast, no MpFV reads were detected in aphids that had acquired PLRV from infected plants or artificial diet sachets containing purified virions. While the titer of M. persicae densovirus (MpDNV) was previously reported to be regulated by expression of the PLRV silencing suppressor protein P0, P0 had no effect on MpFV titer in the aphid. MpFV was transmitted 100% vertically to the offspring, and exhibited tissue tropisms for the body rather than the head. By artificial diet assays, other aphid species, including Aphis gossypii (cotton aphid), Schizaphis graminum (greenbug aphid), Rhopalosiphum padi (bird cherry-oat aphid), and R. maidis (corn leaf aphid), acquired the MpFV. These findings further support the idea that PLRV suppresses aphid immunity against ISVs, suggest the existence of at least two distinct pathways for PLRV-induced aphid immune system modulation. To test whether other circulative plant pathogens suppress insect anti-viral immunity against insect-specific flaviviruses, we quantified the small RNA response of Diaphorina citri, vector of "Candidatus Liberibacter asiaticus" (CLas) associated with citrus greening disease and showed that CLas also suppresses D. citri anti-viral immunity against D. citri-like flavivirus (DcLFV). These data reveal an evolutionary conserved, unexpected role for diverse circulative plant pathogens in modulating anti-viral immunity in hemipteran vectors.

microbiology↗

Mapping Vector Field of Single Cells

Single-cell RNA-seq, together with RNA velocity and metabolic labeling, reveals cellular states and transitions at unprecedented resolution. Fully exploiting these data, however, requires dynamical models capable of predicting cell fate and unveiling the governing regulatory mechanisms. Here, we introduce dynamo, an analytical framework that reconciles intrinsic splicing and labeling kinetics to estimate absolute RNA velocities, reconstructs velocity vector fields that predict future cell fates, and finally employs differential geometry analyses to elucidate the underlying regulatory networks. We applied dynamo to a wide range of disparate biological processes including prediction of future states of differentiating hematopoietic stem cell lineages, deconvolution of glucocorticoid responses from orthogonal cell-cycle progression, characterization of regulatory networks driving zebrafish pigmentation, and identification of possible routes of resistance to SARS-CoV-2 infection. Our work thus represents an important step in going from qualitative, metaphorical conceptualizations of differentiation, as exemplified by Waddingtons epigenetic landscape, to quantitative and predictive theories.

systems biology↗

The murine transcriptome reveals global aging nodes with organ-specific phase and amplitude

Aging is the single greatest cause of disease and death worldwide, and so understanding the associated processes could vastly improve quality of life. While the field has identified major categories of aging damage such as altered intercellular communication, loss of proteostasis, and eroded mitochondrial function1, these deleterious processes interact with extraordinary complexity within and between organs. Yet, a comprehensive analysis of aging dynamics organism-wide is lacking. Here we performed RNA-sequencing of 17 organs and plasma proteomics at 10 ages across the mouse lifespan. We uncover previously unknown linear and non-linear expression shifts during aging, which cluster in strikingly consistent trajectory groups with coherent biological functions, including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Remarkably, these gene sets are expressed similarly across tissues, differing merely in age of onset and amplitude. Especially pronounced is widespread immune cell activation, detectable first in white adipose depots in middle age. Single-cell RNA-sequencing confirms the accumulation of adipose T and B cells, including immunoglobulin J-expressing plasma cells, which also accrue concurrently across diverse organs. Finally, we show how expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to aging of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of aging, thereby providing a foundation to track systemic sources of declining health at old age.

genomics↗