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1.
J Biol Chem ; : 107701, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39173946

RESUMO

The introduction of combined antiretroviral therapy (cART) has greatly improved the quality of life of human immunodeficiency virus type 1 (HIV-1)-infected individuals. Nonetheless, the ever-present desire to seek out a full remedy for HIV-1 infections makes the discovery of novel antiviral medication compelling. Owing to this, a new late-stage inhibitor, Lenacapavir/Sunlenca, an HIV multi-phase suppressor, was clinically authorized in 2022. Besides unveiling cutting-edge antivirals inhibiting late-stage proteins or processes, newer therapeutics targeting host restriction factors hold promise for the curative care of HIV-1 infections. Notwithstanding, bone marrow stromal antigen 2 (BST2)/Tetherin/CD317/HM1.24, which entraps progeny virions is an appealing HIV-1 therapeutic candidate. In this study, a novel drug screening system was established, using the Jurkat/Vpr-HiBiT T cells, to identify drugs that could obstruct HIV-1 release; the candidate compounds were selected from the Ono Pharmaceutical compound library. Jurkat T cells expressing Vpr-HiBiT were infected with NL4-3, and the amount of virus release was quantified indirectly by the amount of Vpr-HiBiT incorporated into the progeny virions. Subsequently, the candidate compounds that suppressed viral release were used to synthesize the heterocyclic compound, HT-7, which reduces HIV-1 release with less cellular toxicity. Notably, HT-7 increased cell surface BST2 coupled with HIV-1 release reduction in Jurkat cells but not Jurkat/KO-BST2 cells. Seemingly, HT-7 impeded simian immunodeficiency virus (SIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) release. Concisely, these results suggest that the reduction in viral release, following HT-7 treatment, resulted from the modulation of cell surface expression of BST2 by HT-7.

2.
Reprod Domest Anim ; 59(3): e14550, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38465367

RESUMO

Two male Japanese Black calves developed an enlarged scrotum and testis. Orchiectomy was performed and pus was collected during surgery. After removal of the testis, bacteriological and histopathological examinations were conducted to investigate the cause and confirm the diagnosis. Based on the results obtained, both cases were diagnosed with epididymitis caused by an infection with Pasteurella multocida. This is the first study to show that P. multocida causes epididymitis in male calves. Further studies are required to clarify the details underlying the infection of calves with P. multocida.


Assuntos
Doenças dos Bovinos , Epididimite , Pasteurella multocida , Bovinos , Animais , Masculino , Epididimite/veterinária , Testículo
3.
Int J Mol Sci ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38279353

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 19 (COVID-19) and employs angiotensin-converting enzyme 2 (ACE2) as the receptor. Although the expression of ACE2 is crucial for cellular entry, we found that the interaction between ACE2 and the Spike (S) protein in the same cells led to its downregulation through degradation in the lysosomal compartment via the endocytic pathway. Interestingly, the ability of the S protein from previous variants of concern (VOCs) to downregulate ACE2 was variant-dependent and correlated with disease severity. The S protein from the Omicron variant, associated with milder disease, exhibited a lower capacity to downregulate ACE2 than that of the Delta variant, which is linked to a higher risk of hospitalization. Chimeric studies between the S proteins from the Delta and Omicron variants revealed that both the receptor-binding domain (RBD) and the S2 subunit played crucial roles in the reduced ACE2 downregulation activity observed in the Omicron variant. In contrast, three mutations (L452R/P681R/D950N) located in the RBD, S1/S2 cleavage site, and HR1 domain were identified as essential for the higher ACE2 downregulation activity observed in the Delta variant compared to that in the other VOCs. Our results suggested that dysregulation of the renin-angiotensin system due to the ACE2 downregulation activity of the S protein of SARS-CoV-2 may play a key role in the pathogenesis of COVID-19.


Assuntos
Enzima de Conversão de Angiotensina 2 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/metabolismo , COVID-19/virologia , Mutação , Ligação Proteica , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo
4.
Vet Res Commun ; 48(4): 2295-2308, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38748076

RESUMO

General anesthesia in calves is easier to perform under field conditions, total intravenous anesthesia (TIVA) than using inhalation anesthesia. In the present study, cardiopulmonary function, anesthetic effects, quality of arousal, hematology, and blood biochemistry were assessed during continuous infusion of a combination solution of 0.01% xylazine, 0.001% butorphanol, and 0.2% propofol (XBP) at doses of 6 (G6; 10 µg/kg/min xylazine, 1 µg/kg/min butorphanol, 200 µg/kg/min propofol) and 9 mL/kg/h (G9; 15 µg/kg/min xylazine, 1.5 µg/kg/min butorphanol 300 µg/kg/min propofol). For both groups, five castrated Holstein calves received intravenous injections of xylazine (0.2 mg/kg) and propofol (2 mg/kg), followed by a continuous infusion of XBP for 60 min to maintain anesthesia. Respiratory management consisted of tracheal intubation followed by spontaneous inhalation of pure oxygen. Cardiopulmonary, anesthesia, hematology, and blood biochemistry variables were assessed at rest (baseline) and every 5 or 15 min after the start of the XBP infusion. Quality of arousal was assessed based on the swallowing reflex recovery time from the stop of XBP infusion, and the sternal position time and standing time after atipamezole administration. XBP produced adequate sedation, analgesia, and muscle relaxation in all calves and maintained stable anesthesia for 60 min. As XBP infusion time passed, rectal temperature and heart rate became lower, and mean arterial blood pressure increased. In both groups, hematologic and blood biochemical effects were mild. The quality of arousal was not different, and all calves were standing. The results of the present study suggested that XBP is useful for TIVA in calves.


Assuntos
Butorfanol , Propofol , Xilazina , Animais , Bovinos/fisiologia , Xilazina/farmacologia , Xilazina/administração & dosagem , Butorfanol/administração & dosagem , Butorfanol/farmacologia , Propofol/administração & dosagem , Propofol/farmacologia , Masculino , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/farmacologia , Infusões Intravenosas/veterinária , Frequência Cardíaca/efeitos dos fármacos , Nível de Alerta/efeitos dos fármacos , Anestesia Intravenosa/veterinária , Anestesia Intravenosa/métodos
5.
J Vet Med Sci ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39111845

RESUMO

In cattle, bovine respiratory syncytial virus (BRSV) is associated with secondary bacterial infections; however, the mechanisms of the interaction between BRSV and bacteria are unclear. Trueperella pyogenes (T. pyogenes) causes pneumonia in cattle and is involved in secondary infections following viral infections. In this study, we evaluated the effect of BRSV infection on the adhesion of T. pyogenes to BRSV-infected cells. BRSV infection significantly enhanced the adhesion of T. pyogenes to cells in a multiplicity of infection- and time-dependent manner. The BRSV-mediated change in the adhesion of T. pyogenes was widely observed in various cell types and bacterial strains. The results from the gentamicin protection assay showed that BRSV infection did not affect the intracellular invasion ability of T. pyogenes. Furthermore, adhesion assays conducted using BRSV G protein-expressing cells and anti-BRSV G antibodies revealed that the increased adhesion of T. pyogenes to cells was mediated by the G protein of BRSV. In addition, immunofluorescence assay revealed the colocalization of BRSV G protein and T. pyogenes. Thus, BRSV infection can potentially lead to bovine respiratory disease complex by promoting the adhesion of T. pyogenes to the infected cells.

6.
Viruses ; 16(7)2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39066304

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has acquired multiple mutations since its emergence. Analyses of the SARS-CoV-2 genomes from infected patients exhibit a bias toward C-to-U mutations, which are suggested to be caused by the apolipoprotein B mRNA editing enzyme polypeptide-like 3 (APOBEC3, A3) cytosine deaminase proteins. However, the role of A3 enzymes in SARS-CoV-2 replication remains unclear. To address this question, we investigated the effect of A3 family proteins on SARS-CoV-2 replication in the myeloid leukemia cell line THP-1 lacking A3A to A3G genes. The Wuhan, BA.1, and BA.5 variants had comparable viral replication in parent and A3A-to-A3G-null THP-1 cells stably expressing angiotensin-converting enzyme 2 (ACE2) protein. On the other hand, the replication and infectivity of these variants were abolished in A3A-to-A3G-null THP-1-ACE2 cells in a series of passage experiments over 20 days. In contrast to previous reports, we observed no evidence of A3-induced SARS-CoV-2 mutagenesis in the passage experiments. Furthermore, our analysis of a large number of publicly available SARS-CoV-2 genomes did not reveal conclusive evidence for A3-induced mutagenesis. Our studies suggest that A3 family proteins can positively contribute to SARS-CoV-2 replication; however, this effect is deaminase-independent.


Assuntos
Desaminases APOBEC , COVID-19 , Citidina Desaminase , SARS-CoV-2 , Replicação Viral , Humanos , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , SARS-CoV-2/metabolismo , Desaminases APOBEC/metabolismo , Desaminases APOBEC/genética , COVID-19/virologia , COVID-19/metabolismo , Citidina Desaminase/metabolismo , Citidina Desaminase/genética , Células THP-1 , Mutação , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Genoma Viral
7.
Vet Res Commun ; 48(3): 1915-1920, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38443589

RESUMO

Nasal granuloma in cattle results from inflammation within, and attendant proliferation of, the nasal mucosa possibly in response to an allergic response. However, the relationship between nasal granuloma and allergies remains unclear. Furthermore, severe cases have a poor prognosis because there is currently no effective treatment. Herein, we report three cases of nasal granuloma with severe stertorous breathing that were treated surgically. We also conducted an allergological exploration. Following surgical removal clinical signs did not recur in two of the three cases; however, stertorous breathing persisted in one case, and the cow was sacrificed 4 months later. A histopathological examination revealed that all nasal granulomas featured varying infiltrations of macrophages eosinophils, mast cells, and lymphocytes. The number of mast cells and the proportion of these cells that had degranulated were significantly higher in the granulomas than in normal nasal mucosae. In addition, serum histamine levels were higher in nasal granuloma cases than in normal cows, although serum immunoglobulin E levels were similar, and lymphocyte infiltration in the submucosal layer suggested type I and type IV allergies. Collectively, the results indicate the efficacy of complete surgical curettage for the treatment of allergic nasal granuloma in cattle. Further studies are required to identify the causes and risk factors of allergic nasal granuloma in cows.


Assuntos
Doenças dos Bovinos , Granuloma , Animais , Bovinos , Feminino , Doenças dos Bovinos/cirurgia , Doenças dos Bovinos/patologia , Granuloma/veterinária , Granuloma/cirurgia , Granuloma/patologia , Doenças Nasais/veterinária , Doenças Nasais/cirurgia , Doenças Nasais/patologia , Imunoglobulina E/sangue , Mucosa Nasal/cirurgia , Mucosa Nasal/patologia
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