Biology subjects

Luo, M.-H.

Publications and source records attributed to Luo, M.-H..

3 recordsLinked to original sources

bioRxiv2020

Human Cytomegalovirus Drives WDR5 to the Virion Assembly Compartment to Facilitate Virion Assembly

We previously reported that human cytomegalovirus (HCMV) utilizes the cellular protein WDR5 to facilitate capsid nuclear egress. Here, we further show that HCMV infection drives WDR5 to the perinuclear region by a mechanism that requires viral replication and intact microtubules. WDR5 accumulated in the virion assembly compartment (vAC) and co-localized with vAC markers of gamma-tubulin ({gamma}-tubulin), early endosomes, and viral vAC marker proteins pp65, pp28, and glycoprotein B (gB). WDR5 interacted with multiple virion proteins, including MCP, pp150, pp65, pIRS1, and pTRS1, which may explain the increasing WDR5 accumulation in the vAC during infection. WDR5 was then incorporated into HCMV virions and localized to the tegument layer, as demonstrated by fractionation and immune-gold electron microscopy. Thus, WDR5 is driven to the vAC and incorporated into virions, suggesting that WDR5 facilitates HCMV replication at later stage of virion assembly besides the capsid nuclear egress stage. These data highlight that WDR5 is a potential target for antiviral therapy. ImportanceHuman cytomegalovirus (HCMV) has a large (~235-kb) genome that contains over 170 ORFs and exploits numerous cellular factors to facilitate its replication. In the late phase of HCMV infection cytoplasmic membranes are profoundly reconfigured to establish the virion assembly compartment (vAC), which is important for efficient assembly of progeny virions. We previously reported that WDR5 promotes HCMV nuclear egress. Here, we show that WDR5 is further driven to the vAC and incorporated into virions, perhaps to facilitate efficient virion maturation. This work identified potential roles for WDR5 in HCMV replication in the cytoplasmic stages of virion assembly. Taken together, WDR5 plays a critical role in HCMV capsid nuclear egress and is important for virion assembly, and thus is a potential target for antiviral treatment of HCMV-associated diseases.

pathology↗

bioRxiv2020

Superior Colliculus-Projected GABAergic Retinal Ganglion Cells Mediate Looming-Evoked Flight Response

The looming stimulus-evoked flight response is an experimental paradigm for studying innate defensive behaviors. However, how the visual looming stimulus is transmitted from the retina to the brain remains poorly understood. Here, we report that superior colliculus (SC)-projecting RGCs transmit the looming signal from the retina to the brain to mediate the looming-evoked flight behavior by releasing GABA. In the mouse retina, GABAergic RGCs are capable of projecting to many brain areas, including the SC. Superior colliculus (SC)-projecting GABAergic RGCs (spgRGCs) are mono-synaptically connected to the parvalbumin-positive SC neurons known to be required for the looming-evoked flight response. Optogenetic activation of spgRGCs triggers GABA-mediated inhibition in SC neurons. The ablation or silence of spgRGCs compromises looming-evoked flight response but not image-forming functions. Therefore, this study shows that spgRGCs control the looming-evoked flight response by regulating SC neurons via GABA, providing novel insight into the regulation of innate defensive behaviors.

neuroscience↗

bioRxiv2018

Human Cytomegalovirus Immediate-Early 1 Protein Causes Loss of SOX2 from Neural Progenitor Cells by Trapping Unphosphorylated STAT3 in the Nucleus

The mechanisms underlying neurodevelopmental damage caused by virus infections remain poorly defined. Congenital human cytomegalovirus (HCMV) infection is the leading cause of fetal brain development disorders. Previous work has linked HCMV to perturbations of neural cell fate, including premature differentiation of neural progenitor cells (NPCs). Here we show that HCMV infection of NPCs results in the loss of the SOX2 protein, a key pluripotency-associated transcription factor. SOX2 depletion maps to the HCMV major immediate-early (IE) transcription unit and is individually mediated by the IE1 and IE2 proteins. IE1 causes SOX2 down-regulation by promoting the nuclear accumulation and inhibiting the phosphorylation of STAT3, a transcriptional activator of SOX2 expression. Deranged signaling resulting in depletion of a critical stem cell protein is an unanticipated mechanism by which the viral major IE proteins may contribute to brain development disorders caused by congenital HCMV infection.\n\nIMPORTANCEHuman cytomegalovirus (HCMV) infections are a leading cause of brain damage, hearing loss and other neurological disabilities in children. We report that the HCMV proteins known as IE1 and IE2 target expression of human SOX2, a central pluripotency-associated transcription factor that governs neural progenitor cell (NPC) fate and is required for normal brain development. Both during HCMV infection and when expressed alone, IE1 causes the loss of SOX2 from NPCs. IE1 mediates SOX2 depletion by targeting STAT3, a critical upstream regulator of SOX2 expression. Our findings reveal an unanticipated mechanism by which a common virus may cause damage to the developing nervous system and suggest novel targets for medical intervention.

microbiology↗