SARS-CoV-2 nucleocapsid induces hyperinflammation and vascular leakage through the Toll-like receptor signaling axis in macrophages.

Tens of thousands of severe COVID-19 cases are hospitalized weekly in the U.S., often driven by an imbalance between antiviral responses and inflammatory signaling, leading to uncontrolled cytokine secretion.

Coronavirus protein interaction mapping in bat and human cells identifies molecular and genetic switches for immune evasion and replication.

Coronaviruses, including SARS-CoV-2, can cause severe disease in humans, whereas reservoir hosts like bats remain asymptomatic. To investigate how host-specific protein-protein interactions (PPIs) influence infection, we generated comparative PPI maps for SARS-CoV-2 and its bat-origin relative RaTG13 using affinity purification-mass spectrometry (AP-MS) in human and (RFe) bat cells. This approach identified both conserved and virus- and host-specific interactions that regulate infection dynamics.

Paracrine Signals from HIV-1 Infected Immune Cells Reprogram Cervical Cancer Pathways.

Persistent infection with human papillomavirus (HPV) is the primary cause of cervical cancer worldwide. Notably, women co-infected with HPV and human immunodeficiency virus type 1 (HIV-1) have a six-fold higher lifetime risk of developing cervical cancer compared to those without HIV, even when adhering to antiretroviral therapy (ART) and achieving T-cell reconstitution. While chronic HIV-1 infection is known to cause inflammation, how paracrine signals from immune cells alter signaling in cervical cells remain poorly understood.

Unflavored electronic cigarette exposure induces alterations in airway ciliary structure and function.

Electronic cigarettes (e-cigs) have been introduced as a safer alternative to traditional combustible cigarettes and have been growing in popularity. E-cig e-liquids all contain the carrier compounds, vegetable glycerin (VG), propylene glycol (PG), and nicotine, together with different flavors, but the effects of inhalation of these compounds on the airway are not well understood. This study investigates the effects of e-cig exposure on primary human airway epithelial cells grown in air-liquid interface (ALI) cultures, specifically focusing on mucociliary clearance, the lung's primary host defense mechanism whereby pathogens and particles trapped by mucus are cleared by unidirectional beating by ciliated cells.

HIV Vpr activates a nucleolar-specific ATR pathway to degrade the nucleolar stress sensor CCDC137.

The lentiviral accessory protein Vpr engages an extensive network of cellular pathways to drive diverse host consequences. Of its many phenotypes, CRL4A-E3 ubiquitin ligase complex co-option, DNA damage response (DDR) engagement, and G2/M arrest are conserved and thus proposed to be functionally important. How Vpr effects these functions and whether they explain how Vpr dysregulates additional cellular pathways remain unclear.

Drug screen reveals new potent host-targeted antivirals against Mpox virus.

Mpox virus (MPXV), a re-emerging zoonotic threat, has caused outbreaks in non-endemic regions through respiratory, sexual, and close-contact transmission. The increased transmissibility of Clade IIb fueled the 2022 global outbreak, with 2024 Clade Ib spread in the Democratic Republic of Congo further escalating concern. Both outbreaks were declared public health emergencies by the WHO.

Global Landscape of Human Kinase Motifs in Viral Proteomes.

The successful establishment of infection relies on an ability to sense and adapt to the host signaling state. One key mechanism of virus-host sensing is host-mediated post-translational modifications of viral proteins. While viral protein phosphorylation by host kinases is known to modulate viral functions, the global prevalence of kinase motifs across diverse viruses, and the signaling pathways they reflect, remains to be systematically explored.

Drug screen reveals new potent host-targeted antivirals against Mpox virus.

Mpox virus (MPXV), a re-emerging zoonotic threat, has caused outbreaks in non-endemic regions through respiratory, sexual, and close-contact transmission. The increased transmissibility of Clade IIb fueled the 2022 global outbreak, with 2024 Clade Ib spread in the Democratic Republic of Congo further escalating concern. Both outbreaks were declared public health emergencies by the WHO.

Malaria exposure remodels the plasma proteome of Ghanaian children.

Background: Malaria, caused by Plasmodium falciparum, remains a major public health burden causing ~ 200 million deaths annually, especially among children. Although the lack of an effective vaccine has hindered malaria elimination, studies have reported on individuals acquiring natural immunity to malaria in the context of high malaria exposure. However, the immune correlates of protection in these people who acquire natural immunity against malaria are poorly understood.

Old World alphaviruses use distinct mechanisms to infect brain microvascular endothelial cells for neuroinvasion.

Several alphaviruses bypass the blood-brain barrier (BBB), causing debilitating or fatal encephalitis. Sindbis virus (SINV) has been extensively studied to understand alphavirus neuropathogenesis; yet the molecular details of neuroinvasion at the BBB remain poorly understood. We investigated alphavirus-BBB interactions by pairing a physiologically relevant, human pluripotent stem cell derived model of brain microvascular endothelial cells (BMECs) with SINV strains of opposite neuroinvasiveness.

PhosNetVis: A web-based tool for fast kinase-substrate enrichment analysis and interactive 2D/3D network visualizations of phosphoproteomics data.

Protein phosphorylation involves the reversible modification of a protein (substrate) residue by another protein (kinase). Liquid chromatography-mass spectrometry studies are rapidly generating massive protein phosphorylation datasets across multiple conditions. Researchers then must infer kinases responsible for changes in phosphosites of each substrate.

SARS-CoV-2 evolution balances conflicting roles of N protein phosphorylation.

All lineages of SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, contain mutations between amino acids 199 and 205 in the nucleocapsid (N) protein that are associated with increased infectivity. The effects of these mutations have been difficult to determine because N protein contributes to both viral replication and viral particle assembly during infection. Here, we used single-cycle infection and virus-like particle assays to show that N protein phosphorylation has opposing effects on viral assembly and genome replication.

Interaction of chikungunya virus glycoproteins with macrophage factors controls virion production.

Despite their role as innate sentinels, macrophages can serve as cellular reservoirs of chikungunya virus (CHIKV), a highly-pathogenic arthropod-borne alphavirus that has caused large outbreaks among human populations. Here, with the use of viral chimeras and evolutionary selection analysis, we define CHIKV glycoproteins E1 and E2 as critical for virion production in THP-1 derived human macrophages. Through proteomic analysis and functional validation, we further identify signal peptidase complex subunit 3 (SPCS3) and eukaryotic translation initiation factor 3 subunit K (eIF3k) as E1-binding host proteins with anti-CHIKV activities.

PhosNetVis: A web-based tool for fast kinase-substrate enrichment analysis and interactive 2D/3D network visualizations of phosphoproteomics data.

Protein phosphorylation involves the reversible modification of a protein (substrate) residue by another protein (kinase). Liquid chromatography-mass spectrometry studies are rapidly generating massive protein phosphorylation datasets across multiple conditions. Researchers then must infer kinases responsible for changes in phosphosites of each substrate.

Mapping Differential Protein-Protein Interaction Networks using Affinity Purification Mass Spectrometry.

Proteins congregate into complexes to perform fundamental cellular functions. Phenotypic outcomes, in health and disease, are often mechanistically driven by the remodeling of protein complexes by protein-coding mutations or cellular signaling changes in response to molecular cues. Here, we present an affinity purification-mass spectrometry (APMS) proteomics protocol to quantify and visualize global changes in protein-protein interaction (PPI) networks between pairwise conditions.

CRISPR-Cas9 screen of E3 ubiquitin ligases identifies TRAF2 and UHRF1 as regulators of HIV latency in primary human T cells.

Unlabelled: During HIV infection of CD4+ T cells, ubiquitin pathways are essential to viral replication and host innate immune response; however, the role of specific E3 ubiquitin ligases is not well understood. Proteomics analyses identified 116 single-subunit E3 ubiquitin ligases expressed in activated primary human CD4+ T cells. Using a CRISPR-based arrayed spreading infectivity assay, we systematically knocked out 116 E3s from activated primary CD4+ T cells and infected them with NL4-3 GFP reporter HIV-1.

A foundational atlas of autism protein interactions reveals molecular convergence.

Translating high-confidence (hc) autism spectrum disorder (ASD) genes into viable treatment targets remains elusive. We constructed a foundational protein-protein interaction (PPI) network in HEK293T cells involving 100 hcASD risk genes, revealing over 1,800 PPIs (87% novel). Interactors, expressed in the human brain and enriched for ASD but not schizophrenia genetic risk, converged on protein complexes involved in neurogenesis, tubulin biology, transcriptional regulation, and chromatin modification.

Hepatitis C virus infects and perturbs liver stem cells.

The hepatitis C virus (HCV) causes liver disease, affecting millions. Even though we have effective antivirals that cure HCV, they cannot stop terminal liver disease. We used an adult stem cell-derived liver organoid system to understand how HCV infection leads to the progression of terminal liver disease.

Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets.

Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases.

Hyperphosphorylation of BCL-2 family proteins underlies functional resistance to venetoclax in lymphoid malignancies.

The B cell leukemia/lymphoma 2 (BCL-2) inhibitor venetoclax is effective in chronic lymphocytic leukemia (CLL); however, resistance may develop over time. Other lymphoid malignancies such as diffuse large B cell lymphoma (DLBCL) are frequently intrinsically resistant to venetoclax. Although genomic resistance mechanisms such as BCL2 mutations have been described, this probably only explains a subset of resistant cases.

Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes several proteins that inhibit host interferon responses. Among these, ORF6 antagonizes interferon signaling by disrupting nucleocytoplasmic trafficking through interactions with the nuclear pore complex components Nup98-Rae1. However, the roles and contributions of ORF6 during physiological infection remain unexplored.

SARS-CoV-2 variants evolve convergent strategies to remodel the host response.

SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions.

Defining blood-induced microglia functions in neurodegeneration through multiomic profiling.

Blood protein extravasation through a disrupted blood-brain barrier and innate immune activation are hallmarks of neurological diseases and emerging therapeutic targets. However, how blood proteins polarize innate immune cells remains largely unknown. Here, we established an unbiased blood-innate immunity multiomic and genetic loss-of-function pipeline to define the transcriptome and global phosphoproteome of blood-induced innate immune polarization and its role in microglia neurotoxicity.