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1. ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome

   https://doi.org/10.1126/sciadv.abl8213  

   Baker, Alexander T.; Boyd, Ryan J.; Sarkar, Daipayan; Teijeira-Crespo, Alicia; Chan, Chun Kit; Bates, Emily; Waraich, Kasim; Vant, John; Wilson, Eric; Truong, Chloe D.; et al (December 2021, Science Advances)

   Vaccines derived from chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 26 (HAdV-D26), and human adenovirus type 5 (HAdV-C5) are critical in combatting the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic. As part of the largest vaccination campaign in history, ultrarare side effects not seen in phase 3 trials, including thrombosis with thrombocytopenia syndrome (TTS), a rare condition resembling heparin-induced thrombocytopenia (HIT), have been observed. This study demonstrates that all three adenoviruses deployed as vaccination vectors versus SARS-CoV-2 bind to platelet factor 4 (PF4), a protein implicated in the pathogenesis of HIT. We have determined the structure of the ChAdOx1 viral vector and used it in state-of-the-art computational simulations to demonstrate an electrostatic interaction mechanism with PF4, which was confirmed experimentally by surface plasmon resonance. These data confirm that PF4 is capable of forming stable complexes with clinically relevant adenoviruses, an important step in unraveling the mechanisms underlying TTS. 

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2. Direct detection of human adenovirus or SARS-CoV-2 with ability to inform infectivity using DNA aptamer-nanopore sensors

   https://doi.org/10.1126/sciadv.abh2848  

   Peinetti, Ana S.; Lake, Ryan J.; Cong, Wen; Cooper, Laura; Wu, Yuting; Ma, Yuan; Pawel, Gregory T.; Toimil-Molares, María Eugenia; Trautmann, Christina; Rong, Lijun; et al (September 2021, Science Advances)

   Viral infections are a major global health issue, but no current method allows rapid, direct, and ultrasensitive quantification of intact viruses with the ability to inform infectivity, causing misdiagnoses and spread of the viruses. Here, we report a method for direct detection and differentiation of infectious from noninfectious human adenovirus and SARS-CoV-2, as well as from other virus types, without any sample pretreatment. DNA aptamers are selected from a DNA library to bind intact infectious, but not noninfectious, virus and then incorporated into a solid-state nanopore, which allows strong confinement of the virus to enhance sensitivity down to 1 pfu/ml for human adenovirus and 1 × 10 4 copies/ml for SARS-CoV-2. Applications of the aptamer-nanopore sensors in different types of water samples, saliva, and serum are demonstrated for both enveloped and nonenveloped viruses, making the sensor generally applicable for detecting these and other emerging viruses of environmental and public health concern. 

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3. Human adenovirus serotype 5 infection dysregulates cysteine, purine, and unsaturated fatty acid metabolism in fibroblasts

   https://doi.org/10.1096/fj.202402726R  

   Sanchez, Bailey‐J_C; Ortiz, Rudy_M; Grasis, Juris_A (March 2025, The FASEB Journal)

   Abstract Viral infections can cause cellular dysregulation of metabolic reactions. Viruses alter host metabolism to meet their replication needs. The impact of viruses on specific metabolic pathways is not well understood, even in well‐studied viruses, such as human adenovirus. Adenoviral infection is known to influence cellular glycolysis and respiration; however, global effects on overall cellular metabolism in response to infection are unclear. Furthermore, few studies have employed an untargeted approach, combining emphasis on viral dosage and infection. To address this, we employed untargeted metabolomics to quantify the dynamic metabolic shifts in fibroblasts infected with human adenovirus serotype 5 (HAdV‐5) at three dosages (0.5, 1.0, and 2.0 multiplicity of infection [MOI]) and across 4 time points (6‐, 12‐, 24‐, and 36‐h post‐infection [HPI]). The greatest differences in individual metabolites were observed at 6‐ and 12‐h post‐infection, correlating with the early phase of the HAdV‐5 infection cycle. In addition to its effects on glycolysis and respiration, adenoviral infection downregulates cysteine and unsaturated fatty acid metabolism while upregulating aspects of purine metabolism. These results reveal specific metabolic pathways dysregulated by adenoviral infection and the associated dynamic shifts in metabolism, suggesting that viral infections alter energetics via profound changes in lipid, nucleic acid, and protein metabolism. The results revealed previously unconsidered metabolic pathways disrupted by HAdV‐5 that can alter cellular metabolism, thereby prompting further investigation into HAdV mechanisms and antiviral targeting. 

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4. Enteric and indicator virus removal by surface flow wetlands

   Rachmadi, A.T.; Kitajima, M.L.; Pepper, I.L.; Gerba, C.P. (January 2016, Science of the total environment)

   We investigated the occurrence and attenuation of several human enteric viruses (i.e., norovirus, adenovirus,Aichi virus 1, polyomaviruses, and enterovirus) as well as a plant virus, pepper mild mottle virus (PMMoV), at two surface flow wetlands in Arizona. The retention time in one of the wetlands was seven days, whereas in the otherwetland it could not be defined.Water sampleswere collected at the inlet and outlet fromthewetlands over nine months, and concentration of viral genomes was determined by quantitative polymerase chain reaction (qPCR). Of the human enteric viruses tested, adenovirus and Aichi virus 1 were found in the greatest prevalence in treated wastewater (i.e., inlet of thewetlands). Reduction efficiencies of enteric viruses by thewetlands ranged from1 to 3 log10. Polyomaviruseswere generally removed to belowdetection limit, indicating at least 2 to 4 log10 removal. PMMoV was detected in a greater concentration in the inlet of both wetlands for all the viruses tested (104 to 107 genome copies/L), but exhibited little or no removal (1 log10 or less). To determine the factors associated with virus genome attenuation (as determined by qPCR), the persistence of PMMoV and poliovirus type 1 (an enterovirus) was studied in autoclaved and natural wetland water, and deionized water incubated under three different temperatures for 21 days. A combination of elevated water temperature and biological activities reduced poliovirus by 1 to 4 log10, while PMMoV was not significantly reduced during this time period.Overall, PMMoV showed much greater persistence than human viruses in the wetland treatment. 

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5. Extracellular Vesicles: Roles in Human Viral Infections, Immune-Diagnostic, and Therapeutic Applications

   https://doi.org/10.3390/pathogens9121056  

   Ipinmoroti, Ayodeji O.; Matthews, Qiana L. (December 2020, Pathogens)

   Membrane-bound vesicles that are released from cells are increasingly being studied as a medium of intercellular communication, as these act to shuttle functional proteins, such as lipids, DNA, rRNA, and miRNA, between cells during essential physiological processes. Extracellular vesicles (EVs), most commonly exosomes, are consistently produced by virus-infected cells, and they play crucial roles in mediating communication between infected and uninfected cells. Notably, pathophysiological roles for EVs have been established in various viral infections, including human immune deficiency virus (HIV), coronavirus (CoV), and human adenovirus (HAdv). Retroviruses, such as HIV, modulate the production and composition of EVs, and critically, these viruses can exploit EV formation, secretion, and release pathways to promote infection, transmission, and intercellular spread. Consequently, EV production has been investigated as a potential tool for the development of improved viral infection diagnostics and therapeutics. This review will summarize our present knowledge of EV–virus relationships, focusing on their known roles in pathophysiological pathways, immunomodulatory mechanisms, and utility for biomarker discovery. This review will also discuss the potential for EVs to be exploited as diagnostic and treatment tools for viral infection. 

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