Alphaherpesviruses (α-HV) are a large family of double-stranded DNA viruses which cause many human and animal diseases. There are three human α-HVs: Herpes Simplex Viruses (HSV-1 and HSV-2) and Varicella Zoster Virus (VZV). All α-HV have evolved multiple strategies to suppress or exploit host cell innate immune signaling pathways to aid in their infections. All α-HVs initially infect epithelial cells (primary site of infection), and later spread to infect innervating sensory neurons. As with all herpesviruses, α-HVs have both a lytic (productive) and latent (dormant) stage of infection. During the lytic stage, the virus rapidly replicates in epithelial cells before it is cleared by the immune system. In contrast, latent infection in host neurons is a life-long infection. Upon infection of mucosal epithelial cells, herpesviruses immediately employ a variety of cellular mechanisms to evade host detection during active replication. Next, infectious viral progeny bud from infected cells and fuse to neuronal axonal terminals. Here, the nucleocapsid is transportedviasensory neuron axons to the ganglion cell body, where latency is established until viral reactivation. This review will primarily focus on how HSV-1 induces various innate immune responses, including host cell recognition of viral constituents by pattern-recognition receptors (PRRs), induction of IFN-mediated immune responses involving toll-like receptor (TLR) signaling pathways, and cyclic GMP‐AMP synthase stimulator of interferon genes (cGAS-STING). This review focuses on these pathways along with other mechanisms including autophagy and the complement system. We will summarize and discuss recent evidence which has revealed how HSV-1 is able to manipulate and evade host antiviral innate immune responses both in neuronal (sensory neurons of the trigeminal ganglia) and non-neuronal (epithelial) cells. Understanding the innate immune response mechanisms triggered by HSV-1 infection, and the mechanisms of innate immune evasion, will impact the development of future therapeutic treatments.

Viruses are intracellular parasites which lack their own metabolism, so they must hijack host cell metabolic machinery in order to increase the production of energy, proteins, fats, and genetic material necessary to replicate. Using murine herpesvirus 68 (MHV-68) as a model system to understand how similar human gammaherpesviruses cause cancer, we profiled the metabolic changes that occur during lytic MHV-68 infection and replication.

G protein-coupled receptors are endocytosed upon activation and several are active from internal membranes. When activated, glucagon receptor (GCGR) undergoes endocytosis and transits via EEA1-marked endosomes. Endocytosis-dependent induction of gluconeogenic genes in hepatocytes implicates the endosomal signaling paradigm for GCGR.

Mental health interventions can help mitigate the unique challenges that individuals in Science, Technology, Engineering, and Mathematics (STEM) face as they navigate these disciplines. We developed the “Mental Health and Wellness: Our Community and our Identity in STEM” workshop, which emphasizes leveraging our STEM community and promoting self-compassion, to foster a conversation among members of the STEM community on how to support mental health and wellness. This interactive workshop begins with a short lecture to define mental health and wellness and introduce evidence-based methods to increase self-compassion. Participants, who are often from diverse backgrounds and various career stages, then explore case studies that highlight experiences related to mental health across STEM career stages. Pre- and post-assessments of workshop participants suggest that participants had positive shifts in their ability to show compassion toward themselves as well as an increased comfort in discussing mental health within their STEM community. This workshop not only provided participants with practical tools and insights but also cultivated a supportive environment, underscoring the importance of mental health awareness and collective well-being within STEM fields. In this paper, we share tips on how this workshop was executed and lessons we have learned from our years of sharing similar workshops in the broader STEM community. We hope this paper serves as a valuable guide for potential facilitators to initiate conversations about mental health and wellness in their respective STEM spaces.

Gammaherpesviruses (GHVs) represent a global clinical burden as the causative agents of Kaposi’s sarcoma and mononucleosis, among other diseases. Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein–Barr virus (EBV) are the most studied human GHVs, and murine gammaherpesvirus 68 (MHV-68) is a recognized experimental model. GHVs are defined by their modulation of the host cell to establish lifelong latent infections and increase host dysregulation during periodic reactivation. Due to their ubiquitous changes in host cells, systems-level techniques are well-suited to study GHV infections at all stages of the central dogma: genomics, transcriptomics, and proteomics. Furthermore, metabolomics can reveal the final metabolic changes across numerous host cellular pathways. This review assesses the current knowledge on GHV infections gained through omics techniques. We also identify gaps and propose future directions, including the development of new therapeutic strategies. Early omics techniques have characterized large swaths of infection for EBV, KSHV, and MHV-68, revealing conserved genes, homologous transcripts, and proteins. Modern omics techniques have enabled higher-resolution studies, yielding insights into heterogeneity in viral-host gene, transcript, and protein modulation strategies across geographical populations, viral subtypes, inter- and intra-patient infections, and latent and lytic states. The metabolome during GHV infections remains the least understood, but current studies have identified essential modulations of nucleotide, amino acid, and lipid synthesis by EBV, KSHV, and MHV-68. Importantly, the application of integrative omics methods to GHV infections remains a promising direction of study as the increased resolution of modern techniques meets the need for greater understanding of differences in each GHV infection.

Kaposi’s Sarcoma Herpesvirus (KSHV), an enveloped double-stranded DNA virus, is the etiological agent of Kaposi’s sarcoma (KS), an endothelial cell-based tumor. KSHV is a leading cause of infection-related cancers in sub-Saharan Africa and immunocompromised individuals worldwide. Therefore, it is vital to identify the underlying mechanisms of viral infection and transmission to effectively identify specific therapeutic strategies and combat the disease. Here, we demonstrate that KSHV rewires the host cell lipidome during lytic infection. Bulk lipidomic analysis shows significant changes in the abundance of neutral lipids and phospholipids during lytic infection. We further investigated fatty acid-binding proteins (FABPs) to understand the underlying mechanisms that support KSHV pathogenesis. Using the doxycyclin-inducible iSLK.BAC16 cell line, we find that FABP genes are differentially regulated by lytic KSHV infection compared to latent infection. We report that FABP4 is significantly upregulated during lytic infection. Loss of FABP4 during lytic infection does not impact viral gene transcription however, lytic protein translation is reduced. Moreover, our intracellular and extracellular viral titers indicate that FABP4 affects maximal infectious virion production. This study highlights the role of FABP4 and its therapeutic potential as a target that facilitates KSHV infection and pathogenesis.