Risk factors for acute kidney injury in patients hospitalized with COVID-19 / Fatores de risco para lesão renal aguda em pacientes hospitalizados com COVID-19

Abstract Introduction: Acute kidney injury (AKI) occurs frequently in COVID-19 patients and is associated with greater morbidity and mortality. Knowing the risks of AKI allows for identification, prevention, and timely treatment. This study aimed to identify the risk factors associated with AKI in hospitalized patients. Methods: A descriptive, retrospective, cross-sectional, and analytical component study of adult patients hospitalized with COVID-19 from March 1 to December 31, 2020 was carried out. AKI was defined by the creatinine criteria of the KDIGO-AKI guidelines. Information, regarding risk factors, was obtained from electronic medical records. Results: Out of the 934 patients, 42.93% developed AKI, 60.59% KDIGO-1, and 9.9% required renal replacement therapy. Patients with AKI had longer hospital stay, higher mortality, and required more intensive care unit (ICU) admission, mechanical ventilation, and vasopressor support. Multivariate analysis showed that age (OR 1.03; 95% CI 1.02-1.04), male sex (OR 2.13; 95% CI 1.49-3.04), diabetes mellitus (DM) (OR 1.55; 95% CI 1.04-2.32), chronic kidney disease (CKD) (OR 2.07; 95% CI 1.06-4.04), C-reactive protein (CRP) (OR 1.02; 95% CI 1.00-1.03), ICU admission (OR 1.81; 95% CI 1.04-3.16), and vasopressor support (OR 7.46; 95% CI 3.34-16.64) were risk factors for AKI, and that bicarbonate (OR 0.89; 95% CI 0.84-0.94) and partial pressure arterial oxygen/inspired oxygen fraction index (OR 0.99; 95% CI 0.98-0.99) could be protective factors. Conclusions: A high frequency of AKI was documented in COVID-19 patients, with several predictors: age, male sex, DM, CKD, CRP, ICU admission, and vasopressor support. AKI occurred more frequently in patients with higher disease severity and was associated with higher mortality and worse outcomes.

RESUMO Introdução: Lesão renal aguda (LRA) ocorre frequentemente em pacientes com COVID-19 e associa-se a maior morbidade e mortalidade. Conhecer riscos da LRA permite a identificação, prevenção e tratamento oportuno. Este estudo teve como objetivo identificar fatores de risco associados à LRA em pacientes hospitalizados. Métodos: Realizou-se estudo descritivo, retrospectivo, transversal e de componente analítico de pacientes adultos hospitalizados com COVID-19 de 1º de março a 31 de dezembro, 2020. Definiu-se a LRA pelos critérios de creatinina das diretrizes KDIGO-LRA. Informações sobre fatores de risco foram obtidas de prontuários eletrônicos. Resultados: Dos 934 pacientes, 42,93% desenvolveram LRA, 60,59% KDIGO-1 e 9,9% necessitaram de terapia renal substitutiva. Pacientes com LRA apresentaram maior tempo de internação, maior mortalidade e necessitaram de mais internações em UTIs, ventilação mecânica e suporte vasopressor. A análise multivariada mostrou que idade (OR 1,03; IC 95% 1,02-1,04), sexo masculino (OR 2,13; IC 95% 1,49-3,04), diabetes mellitus (DM) (OR 1,55; IC 95% 1,04-2,32), doença renal crônica (DRC) (OR 2,07; IC 95% 1,06-4,04), proteína C reativa (PCR) (OR 1,02; IC 95% 1,00-1,03), admissão em UTI (OR 1,81; IC 95% 1,04-3,16) e suporte vasopressor (OR 7,46; IC 95% 3,34-16,64) foram fatores de risco para LRA, e que bicarbonato (OR 0,89; IC 95% 0,84-0,94) e índice de pressão parcial de oxigênio arterial/fração inspirada de oxigênio (OR 0,99; IC 95% 0,98-0,99) poderiam ser fatores de proteção. Conclusões: Documentou-se alta frequência de LRA em pacientes com COVID-19, com diversos preditores: idade, sexo masculino, DM, DRC, PCR, admissão em UTI e suporte vasopressor. LRA ocorreu mais frequentemente em pacientes com maior gravidade da doença e associou-se a maior mortalidade e piores desfechos.

AAV-delivered hepato-adrenal cooperativity in steroidogenesis: Implications for gene therapy for congenital adrenal hyperplasia.

Despite the availability of life-saving corticosteroids for 70 years, treatment for adrenal insufficiency is not able to recapitulate physiological diurnal cortisol secretion and results in numerous complications. Gene therapy is an attractive possibility for monogenic adrenocortical disorders such as congenital adrenal hyperplasia; however, requires further development of gene transfer/editing technologies and knowledge of the target progenitor cell populations. Vectors based on adeno-associated virus are the leading system for direct in vivo gene delivery but have limitations in targeting replicating cell populations such as in the adrenal cortex. One strategy to overcome this technological limitation is to deliver the relevant adrenocortical gene to a currently targetable organ outside of the adrenal cortex. To explore this possibility, we developed a vector encoding human 21-hydroxylase and directed expression to the liver in a mouse model of congenital adrenal hyperplasia. This extra-adrenal expression resulted in reconstitution of the steroidogenic pathway. Aldosterone and renin levels normalized, and corticosterone levels improved sufficiently to reduce adrenal hyperplasia. This strategy could provide an alternative treatment option for monogenic adrenal disorders, particularly for mineralocorticoid defects. These findings also demonstrate, when targeting the adrenal gland, that inadvertent liver transduction should be precluded as it may confound data interpretation.

Acute-Onset Lower Extremity Weakness and Urinary Retention in a Chronically Immunosuppressed Patient: Diagnosis and Management of Herpes Simplex Virus Type 2 Myelitis.

A 34-year-old immunosuppressed male presented with worsening bilateral lower extremity weakness and urinary retention accompanied by a painless clean-based chancre on his glans penis. Physical examination revealed symmetrically diminished lower extremity weakness most pronounced with hip flexion and knee extension and absent Achilles reflexes. Full MRI spine without contrast was noncontributory. Lumbar puncture showed elevated protein and total nucleated cells with lymphocytic predominance. Both CSF and serum polymerase chain reaction were positive for herpes simplex virus type 2. He received IV methylprednisolone and acyclovir and underwent four months of physical therapy with complete resolution of his neurologic deficits.

Eczema Herpeticum Complicating Atopic Dermatitis: A Rare Presentation.

Atopic dermatitis (AD) has become a global health concern due to an increase in its frequency over the past few decades. This illness not only reduces the quality of life but also imposes a considerable financial burden due to the increased risk of skin infections. This case report explores the presentation of a four-month-old male infant with a personal history of atopic dermatitis that developed yellow scaly lesions on the scalp, which were assumed to be cradle cap. However, there was a clinical worsening of the cutaneous lesions, with the appearance of vesicles, so he was referred to the Pediatric Emergency Room after an urgent dermatology appointment. A blood test was performed, which revealed severe eosinophilia and a slightly increased total IgE. Considering the patient's past medical record of atopic dermatitis and the observable characteristics of the skin rash, there was a strong suspicion of eczema herpeticum (EH). Consequently, intravenous acyclovir treatment was initiated, along with an antibiotic, as there were concerns about a potential secondary infection. He was followed up with a pediatric and dermatology appointment, with a resolution of skin lesions after six weeks. EH is a rare clinical entity, usually caused by herpes simplex virus (HSV) types 1 and 2. It is a clinical entity that, while being uncommon, is one of the few dermatological emergencies responsible for a high morbidity rate, associated with the systemic spread of the viral infection.

Papillary Thyroid Carcinoma With Lymphoepithelial Features and Lacking Association With Epstein-Barr Virus (EBV): A Rare Case.

Papillary thyroid carcinoma (PTC) is the most common primary thyroid malignancy. PTC is diagnosed based on its hallmark nuclear characteristics, but a myriad of histological variants has been identified some of which can be diagnostically challenging due to its rarity and overlapping histomorphology with other entities. We report a rare variant of PTC with lymphoepithelial features which lacked association with Epstein-Barr Virus (EBV). In such cases, a thorough workup to rule out metastasis from other sites should be undertaken.

Peripheral Nerve Stimulation for a Refractory Case of Postherpetic Neuralgia in the Upper Limb: A Case Report.

Postherpetic neuralgia (PHN) is a chronic neuropathic pain syndrome that is a direct consequence of the reactivation of varicella zoster virus (VZV). It manifests as neuropathic pain, which is pain that occurs because of dysfunction or damage of the nerves that carry sensations to the brain, and this typically persists for months to years after herpes zoster. Current conservative management for PHN includes a combination of topical agents (i.e., lidocaine and capsaicin) and systemic therapy (i.e., serotonin and norepinephrine reuptake inhibitors (SNRIs), gabapentin, pregabalin, and opioids). For refractory cases, with persistent intractable pain, more invasive interventional techniques can be used as pain-relieving measures to improve the patient's quality of life. This report presents a patient with upper limb PHN who responded to peripheral nerve stimulation (PNS) after he failed to obtain sufficient pain relief with conservative management.

Recent progress in combination therapy of oncolytic vaccinia virus.

In recent years, oncolytic viruses have emerged as promising agents for treating various cancers. An oncolytic virus is a non-pathogenic virus that, due to genetic manipulation, tends to replicate in and cause lysis of cancerous cells while leaving healthy cells unaffected. Among these viruses, vaccinia virus is an attractive platform for use as an oncolytic platform due to its 190 Kb genome with a high capacity for encoding therapeutic payloads. Combining oncolytic VV therapy with other conventional cancer treatments has been shown to be synergistic and more effective than monotherapies. Additionally, OVV can be used as a vector to deliver therapeutic payloads, alone or in combination with other treatments, to increase overall efficacy. Here, we present a comprehensive analysis of preclinical and clinical studies that have evaluated the efficacy of oncolytic vaccinia viruses in cancer immunotherapy. We discuss the outcomes of these studies, including tumor regression rates, overall survival benefits, and long-term responses. Moreover, we provide insights into the challenges and limitations associated with oncolytic vaccinia virus- based therapies, including immune evasion mechanisms, potential toxicities, and the development of resistance.

The Fixed Dose Combination of Sofosbuvir and Velpatasvir is Safe and Effective in Patients of Chronic Hepatitis C With End-stage Renal Disease.

Background: The burden of hepatitis C virus (HCV) in India is alarming, with a major share of this virus being witnessed in patients with end-stage renal disease (ESRD). A pan-genotypic combination of sofosbuvir and velpatasvir is found to be safe, effective, and economical in resource-constraint countries such as ours. However, there are scanty data on the efficacy and safety of sofosbuvir and velpatasvir combination in patients with ESRD. Hence, we performed this study to evaluate the safety and efficacy of the combination of sofosbuvir and velpatasvir in patients of chronic hepatitis C (CHC) with ESRD. Methods: This is an observational study comprising of 40 CHC patients with ESRD on maintenance hemodialysis. All patients were treated with a fixed-dose combination of sofosbuvir and velpatasvir for 12 weeks in case of non-cirrhotic or compensated cirrhosis and 24 weeks in case of decompensated cirrhosis. The efficacy was assessed by sustained virological response defined by negative HCV RNA at 12 weeks (sustained virological response [SVR] 12) post treatment, and safety was assessed by recording any side-effects of all patients. Results: Out of the 40 patients enrolled in our study, majority were non-cirrhotic (77%), and all were treatment-naive. The mean age was 49.87 ± 12.13 years, and 80% patients were male. The mean baseline HCV RNA was 2.61 ± 7.83 × 106 IU/ml. All the 40 patients (100%) achieved undetectable HCV RNA at the end of treatment; however, 39 patients (97.5%) achieved SVR 12. There was no significant deterioration of estimated glomerular filtration rate (eGFR) after completion of antiviral therapy as compared to the baseline eGFR (13.27 ± 10.32 vs13.54 ± 11.38, P = 0.54). None of the patients reported any serious adverse effects during treatment. Conclusion: The fixed-dose combination of sofosbuvir and velpatasvir is effective and has showed excellent safety profile in patients of CHC with ESRD.

Occupational exposure to Hepatitis B virus, disease burden and pathways for postexposure prophylaxis management: recommendations for healthcare workers in highly endemic settings.

Hepatitis B Virus (HBV) was recognized many decades ago as an important occupational hazard for Health Care Workers (HCWs) globally. HCWs who are directly involved in patient care and are in continuous contact with blood or body fluids have an increased risk of occupationally acquiring the virus. The risk of HCWs in highly endemic areas is greater due to the greater prevalence of infection in the general population. Recommendations are available to guide HBV prevention activities or practices among HCWs. These include the use of the hepatitis B vaccine as a preexposure prophylaxis and the use of hepatitis B immunoglobulin alone or hepatitis B immunoglobulin plus the vaccine as postexposure prophylaxis. The uptake of preexposure prophylaxis has been observed to be low in resource-poor settings where the disease is highly endemic. Postexposure prophylaxis has become the remedy for preventing occupational transmission of HBV in these settings. This review aimed to summarize the available evidence on the risk of transmission of HBV infection, the burden of infection and recommendations for pre- and postexposure prophylaxis for the prevention of occupational acquisition of HBV among HCWs. We conducted a narrative review to summarize the evidence available on the recommended steps of HBV exposure management and the utilization of post-exposure prophylaxis (PEP) for HBV. A comprehensive search was conducted in PubMed, Science Direct, Google Scholar, and Africa Journals Online (AJOL) databases. The keywords used were hepatitis B, hepatitis B virus postexposure prophylaxis, occupational exposures, and recommendations for postexposure to hepatitis B virus. We gleaned evidence from the literature sources and summarized the concepts related to exposure forms, postexposure prophylaxis management pathways and recommendations for the utilization of postexposure prophylaxis among exposed healthcare workers. From the synthesis of evidence, we conclude that HBV infection is a life-threatening condition. However, the disease is preventable by using the HBV vaccine as a preexposure prophylaxis measure. An effective postexposure prophylaxis management program is also available, and the last resort to preventing occupational transmission of HBV among HCWs who non-responders are, or who fail to vaccinate completely against HBV. Irrespective of the availability of these lifesaving interventions, the use of pre- and post-exposure prophylaxis among HCWs in highly endemic regions is suboptimal. Many barriers operating at the individual HCW and health facility levels have been identified as impacting the successful use of HBV preventive measures.

Assessment of knowledge and attitude of cervical cancer among the youths in the Rayalaseema region of Andhra Pradesh - India.

BACKGROUND: India suffers a quarter of the global burden of cervical cancer (CC) but is controllable by taking some precautions. The major issue is the low amount of participation among women in screening and vaccination for disease. The objective of the research is to evaluate knowledge, attitude, and practice (KAP) regarding CC among college going students residing in the Rayalaseema region of Andhra Pradesh-India. MATERIAL AND METHODS: A cross-sectional study was conducted on a total of 380 subjects whose ages ranged from 15 to 25 and older. The questionnaires were circulated through google forms. The socio-demographic variables and KAP levels are represented by descriptive statistics. The Chi-square test is used to determine the relationship between sociodemographic factors and KAP levels. RESULTS: Among 380 subjects, 172 (54.7%) are aware of CC, 71% have poor knowledge, and 20% have good knowledge about CC. More than three-fourths of women 374 (98.4%) are not having regular practice towards CC. CONCLUSION: The awareness about CC is very low in the population, so prevention of CC relies on routine screening, proper vaccination, and treatment. Awareness programs and promoting knowledge about cervical health in social media are required.

MPox Skin Lesions.

Mpox is caused by the Monkeypox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. The Monkeypox virus was first identified as a cause of disease in humans in the 1970s in the Democratic Republic of the Congo. Mpox was considered endemic in several African countries. A global outbreak of Mpox was first recognized in Europe in May 2022 and was declared a public health emergency of international concern on July 23, 2022. The first reported Mpox case in Indonesia was in October 2022 which was identified as an imported case, there were no new confirmed Mpox cases until 13 October 2023. Since then there were 72 cases of confirmed Mpox cases in Indonesia by the end of 2023, distributed across 6 provinces, mostly in the Java island.We present two different spectrums of Mpox skin lesions in patients living with HIV, with a positive polymerase chain reaction test for Mpox. The first patient is a 48-year-old male, who developed a maculopapular lesion, that was initially noticed on the face, the lesions were then spread to the back and hand. He identifies as men who have sex with men and living with HIV for the past 18 years. There were no lesions on the genitalia or mucosa. The second patient is a 28-year-old male, the initial symptom was fever, followed by skin lesions after around 1 week of fever. The lesion initially appears as pustules on the face and then spreads throughout the whole body, the lesions also grow larger and become pseudo-pustules and ulcers. There were also mucosal involvements in the mouth, making oral intake difficult. This patient also identified as men who have sex with men with multiple partners, HIV status was not known at the initial presentation. HIV screening was done with positive results.

Assessment of knowledge and perceptions of human papillomavirus vaccine and its determinants among women who have eligible daughters in Debre Berhan City, Ethiopia: a cross-sectional study.

Introduction: Globally, cervical cancer(CC) is the second most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women. Human papillomavirus (HPV) infection is the leading cause of CC. Persistent infection with HPV accounts for 90% of all CC cases. The human papillomavirus vaccine has the great potential to prevent HPV-related infections for millions of women and men. The current study aimed to assess knowledge and perceptions towards the HPV vaccine and its determinants among women who have eligible daughters in Debre Berhan City, Ethiopia. Methods: A cross-sectional study was conducted from April 2, 2023, to May 15, 2023. A multistage sampling procedure was used to recruit 607 women participants. Descriptive statistics were used to summarize socio-demographic data. Univariable and multivariable binary logistic regression analyses were performed to measure the associations between the dependent and independent variables. A p-value of <0.05 was considered statistically significant. Results: More than three-fourths of the participants, 479 individuals (80%) were currently married, and 243(40.1%) had a diploma or higher education level. Of 456(75.12) participants reported, they had information about cervical cancer. For 449(73.9%) of the participants, television was the main evidence. The majority of 352(59.99%) participants knew the HPV vaccine could be offered to a female child aged 9-14 years old. Only 215(35.4%) participants think the HPV vaccine was safe and effective. Women who had a degree and above educational level were about 9 times more likely to have good knowledge about the HPV vaccine than study participants who did not read and write (AOR=9.21; 95% CI=2.82-12.16; p=0.004). Women who did not have information about the HPV vaccine before this study were about 80% less likely to have a positive perception of the HPV vaccine than participants who had earlier information about the HPV vaccine (AOR=0.8; 95%CI=0.63-0.49; P=003). Conclusion: Women had poor knowledge and perceptions about the HPV vaccine. Maternal marital status, age, and having information about the HPV vaccine were the only predictors of women's knowledge of the HPV vaccine.

Epstein - Barr Virus Salivary Shedding in Patients with Acute Infectious Diseases: A Pilot Study.

Background: Epstein-Barr virus (EBV) is a widely disseminated herpesvirus for which antibodies have been demonstrated in over 90% of adults worldwide. After subclinical primary EBV infections, as well as after infectious mononucleosis, the virus can be shed in saliva for a prolonged period of time. Aim: Diseases and disorders that can induce EBV salivary shedding include mental disorders and sex, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, malaria and HIV infection. Since the occurrence of EBV in saliva during acute infectious diseases has not yet been systematically researched, we aimed to investigate the possible relationship between acute infectious diseases and salivary shedding of EBV. Material and methods: This pilot cross-sectional study included consenting adults hospitalized for acute infectious conditions and their peers free of acute infectious diseases. A total of 40 patients with acute infectious diseases were enrolled, along with 41 adults free of acute infections. Peripheral venous blood samples for serodiagnosis and saliva samples for EBV PCR testing were collected from both groups. We fitted logit and general linear models to proportions and to ln (viral copy counts) to generate adjusted proportions and geometric mean values in the two groups of subjects. We used SAS for Windows 9.4. Results: The most common acute infectious disease was COVID-19 pneumonia, followed by hemorrhagic fever with renal syndrome. Crude proportions of people with positive serological test results and those with saliva viral shedding were similar in the two groups. Conclusions: The presented preliminary data do not indicate acute infectious conditions as a marked "contributor" in increasing salivary EBV shedding.

Extrahepatic Manifestations of Chronic Hepatitis C Virus (HCV) Infection.

Hepatitis C virus (HCV) is a well-recognized, major cause of various liver-related conditions such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Apart from liver disease, chronic HCV infection is also associated with several extrahepatic manifestations that can lead to significant morbidity and mortality. These extrahepatic manifestations include essential mixed cryoglobulinemia (EMC), lymphomas, porphyria cutanea tarda, lichen planus, necrolytic acral erythema, glomerulonephritis, subclinical autoantibody formation, immune thrombocytopenia, thyroid disease, Sjögren's disease/sicca symptoms, diabetes mellitus, ocular diseases, musculoskeletal disorders, cardiovascular diseases, neurocognitive dysfunction, and leukocytoclastic vasculitis. We are presenting a case of chronic HCV infection linked to the extrahepatic manifestations of the disease which can be directly related to HCV or indirectly related to EMC from HCV. An awareness and knowledge of these extrahepatic manifestations will highlight the importance of recognizing the symptoms for an early diagnosis and effective anti-viral treatment in order to improve or resolve the long-term complications of chronic HCV infection.

Evolution of exploitation and replication of giant viruses and virophages.

Tripartite biotic interactions are inherently complex, and the strong interdependence of species and often one-sided exploitation can make these systems vulnerable to extinction. The persistence of species depends then on the balance between exploitation and avoidance of exploitation beyond the point where sustainable resource use is no longer possible. We used this general prediction to test the potential role of trait evolution for persistence in a tripartite microbial system consisting of a marine heterotrophic flagellate preyed upon by a giant virus, which in turn is parasitized by a virophage. Host and virophage may benefit from this interaction because the virophage reduces the harmful effects of the giant virus on the host population and the virophage can persist integrated into the host genome when giant viruses are scarce. We grew hosts and virus in the presence and absence of the virophage over ∼280 host generations and tested whether levels of exploitation and replication in the giant virus and/or virophage population evolved over the course of the experiment, and whether the changes were such that they could avoid overexploitation and extinction. We found that the giant virus evolved toward lower levels of replication and the virophage evolved toward increased replication but decreased exploitation of the giant virus. These changes reduced overall host exploitation by the virus and virus exploitation by the virophage and are predicted to facilitate persistence.

Brain function abnormalities and neuroinflammation in people living with HIV-associated anxiety disorders.

Background: People living with HIV (PLWH) exhibits an increased susceptibility to anxiety disorders, concomitant with heightened vulnerability to aberrant immune activation and inflammatory responses, and endocrine dysfunction. There exists a dearth of scholarly investigations pertaining to the neurological, immune, and endocrine dimensions of HIV-associated anxiety disorders. Method: This study aimed to compare a group of 16 individuals diagnosed with HIV-associated anxiety disorders (HIV ANXs) according to the Diagnostic and statistical manual of mental disorders (5th ed.), with a HIV individual control group (HIV control) of 49 PLWH without mental disorders. Muti-modal magnetic resonance was employed to assess the brain function and structure of both groups. Seed-based functional connectivity (FC) was used to assess the regional intrinsic brain activity and the influence of regional disturbances on FC with other brain regions. Peripheral blood cytokines and chemokines concentrations were measured using liquid chip and ELISA. Results: Amplitude of low-frequency fluctuations in the right inferior temporal gyrus (ITG) was increased. There is a significant decreased regional homogeneity in HIV ANXs in the right superior occipital gyrus (SOG). The right ITG and the right SOG were separately set as the seed brain region of interest (ROI 1 and ROI 2) to be analyzed the FC. FC decreased in HIV ANXs between ROI1 and the right middle occipital gyrus, the right SOG, FC between ROI2 and left ITG increased in HIV ANXs. No significant structural difference was found between two groups. Pro-inflammatory chemokines showed higher levels in the HIV ANXs. Pro-inflammatory cytokines, neurotrophic factors, and endocrine factors were significantly correlated with alterations in brain function. Conclusion: This study suggests that patients with HIV-associated anxiety disorders may exhibit abnormalities in neurologic, immune, and endocrine functioning. Consequently, it is imperative to implement additional screening and intervention measures for anxiety disorders among PLWH.

Differential Contributions of Interferon Classes to Host Inflammatory Responses and Restricting Virus Progeny Production.

Fundamental to mammalian intrinsic and innate immune defenses against pathogens is the production of Type I and Type II interferons, such as IFN-ß and IFN-γ, respectively. The comparative effects of IFN classes on the cellular proteome, protein interactions, and virus restriction within cell types that differentially contribute to immune defenses are needed for understanding immune signaling. Here, a multilayered proteomic analysis, paired with biochemical and molecular virology assays, allows distinguishing host responses to IFN-ß and IFN-γ and associated antiviral impacts during infection with several ubiquitous human viruses. In differentiated macrophage-like monocytic cells, we classified proteins upregulated by IFN-ß, IFN-γ, or pro-inflammatory LPS. Using parallel reaction monitoring, we developed a proteotypic peptide library for shared and unique ISG signatures of each IFN class, enabling orthogonal confirmation of protein alterations. Thermal proximity coaggregation analysis identified the assembly and maintenance of IFN-induced protein interactions. Comparative proteomics and cytokine responses in macrophage-like monocytic cells and primary keratinocytes provided contextualization of their relative capacities to restrict virus production during infection with herpes simplex virus type-1, adenovirus, and human cytomegalovirus. Our findings demonstrate how IFN classes induce distinct ISG abundance and interaction profiles that drive antiviral defenses within cell types that differentially coordinate mammalian immune responses.

Reduced cold tolerance of viral-infected leafhoppers attenuates viral persistent epidemics.

Most arthropod-borne viruses produce intermittent epidemics in infected plants. However, the underlying mechanisms of these epidemics are unclear. Here, we demonstrated that rice stripe mosaic virus (RSMV), a viral pathogen, significantly increases the mortality of its overwintering vector, the leafhopper species Recilia dorsalis. Cold-stress assays indicated that RSMV reduces the cold tolerance of leafhoppers, a process associated with the downregulation of leafhopper cuticular protein genes. An RSMV-derived small RNA (vsiR-t00355379) was found to facilitate the downregulation of a leafhopper endocuticle gene that is mainly expressed in the abdomen (named RdABD-5) and is conserved across dipteran species. The downregulation of RdABD-5 expression in R. dorsalis resulted in fewer and thinner endocuticle lamellae, leading to decreased cold tolerance. This effect was correlated with a reduced incidence rate of RSMV in early-planted rice plants. These findings contribute to our understanding of the mechanism by which viral pathogens reduce cold tolerance in arthropod vectors and suggest an approach to managing the fluctuating prevalence of arboviruses. IMPORTANCE: Increasing arthropod vector dispersal rates have increased the susceptibility of crop to epidemic viral diseases. However, the incidence of some viral diseases fluctuates annually. In this study, we demonstrated that a rice virus reduces the cold tolerance of its leafhopper vector, Recilia dorsalis. This effect is linked to the virus-derived small RNA-mediated downregulation of a gene encoding a leafhopper abdominal endocuticle protein. Consequently, the altered structural composition of the abdominal endocuticle reduces the overwinter survival of leafhoppers, resulting in a lower incidence of RSMV infection in early-planted rice plants. Our findings illustrate the important roles of RNA interference in virus-vector insect-environment interactions and help explain the annual fluctuations of viral disease epidemics in rice fields.

On-The-Spot Sampling and Detection of Viral Particles on Solid Surfaces Using a Sponge Virus Sensor Incorporated with Finger-Press Fluid Release.

This paper presents a sponge-based electrochemical sensor for rapid, on-site collection and analysis of infectious viruses on solid surfaces. The device utilizes a conducting porous sponge modified with graphene, graphene oxide, and specific antibodies. The sponge serves as a hydrophilic porous electrode capable of liquid collection and electrochemical measurements. The device operation involves spraying an aqueous solution on a target surface, swiping the misted surface using the sponge, discharging an electrolyte solution with a simple finger press, and performing in situ incubation and electrochemical measurements. By leveraging the water-absorbing ability of the biofunctionalized conducting sponge, the sensor can effectively collect and quantify virus particles from the surface. The portability of the device is enhanced by introducing a push-release feature that dispenses the liquid electrolyte from a miniature reservoir onto the sensor surface. This reservoir has sharp edges to rupture a liquid sealing film with a finger press. The ability of the device to sample and quantify viral particles is demonstrated by using influenza A virus as the model. The sensor provided a calculated limit of detection of 0.4 TCID50/mL for H1N1 virus, along with a practical concentration range from 1-106 TCID50/mL. Additionally, it achieves a 15% collection efficiency from single-run swiping on a tabletop surface. This versatile device allows for convenient on-site virus detection within minutes, eliminating the need for sample pretreatment and simplifying the entire sample collecting and measuring process. This device presents significant potential for rapid virus detection on solid surfaces.