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Neutralizing antibodies (nAbs) are a critical part of coronavirus disease 2019 (COVID-19) research as they are used to gain insight into the immune response to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infections. Among the technologies available for generating nAbs, DNA-based immunization methods are an alternative to conventional protocols. In this pilot study, we investigated whether DNA-based immunization by needle injection in rabbits was a viable approach to produce a functional antibody response. We demonstrated that three doses of DNA plasmid carrying the gene encoding the full-length spike protein (S) or the receptor binding domain (RBD) of SARS-CoV-2 induced a time-dependent increase in IgG antibody avidity maturation. Moreover, the IgG antibodies displayed high cross neutralization by live SARS-CoV-2 and pseudoviruses neutralization assays. Thus, we established a simple, low cost and feasible DNA-based immunization protocol in rabbits that elicited high IgG avidity maturation and nAbs production against SARS-CoV-2, highlighting the importance of DNA-based platforms for developing new immunization strategies against SARS-CoV-2 and future emerging epidemics. [ABSTRACT FROM AUTHOR]

Background: Multi‐organ damage is a common feature of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, going beyond the initially observed severe pneumonia. Evidence that the testis is also compromised is growing. Objective: To describe the pathological findings in testes from fatal cases of COVID‐19, including the detection of viral particles and antigens, and inflammatory cell subsets. Materials and methods: Postmortem testicular samples were obtained by percutaneous puncture from 11 deceased men and examined by reverse‐transcription polymerase chain reaction (RT‐PCR) for RNA detection and by light and electron microscopy (EM) for SARS‐CoV‐2. Immunohistochemistry (IHC) for the SARS‐CoV‐2 N‐protein and lymphocytic and histiocytic markers was also performed. Results: Eight patients had mild interstitial orchitis, composed mainly of CD68+ and TCD8+ cells. Fibrin thrombi were detected in five cases. All cases presented congestion, interstitial edema, thickening of the tubular basal membrane, decreased Leydig and Sertoli cells with reduced spermatogenesis, and strong expression of vascular cell adhesion molecule (VCAM) in vessels. IHC detected SARS‐Cov‐2 antigen in Leydig cells, Sertoli cells, spermatogonia, and fibroblasts in all cases. EM detected viral particles in the cytoplasm of fibroblasts, endothelium, Sertoli and Leydig cells, spermatids, and epithelial cells of the rete testis in four cases, while RT‐PCR detected SARS‐CoV‐2 RNA in three cases. Discussion and conclusion: The COVID‐19‐associated testicular lesion revealed a combination of orchitis, vascular changes, basal membrane thickening, Leydig and Sertoli cell scarcity, and reduced spermatogenesis associated with SARS‐CoV‐2 local infection that may impair hormonal function and fertility in men. [ABSTRACT FROM AUTHOR]

From 2016 to 2018, an epidemic wave of yellow fever (YF) occurred in Brazil, affecting a large number of Platyrrhini monkeys. Titi monkeys (Callicebus spp.) were severely affected yet pathological characterizations are lacking. This study characterized epizootic YF in 43 titi monkeys (Callicebus spp.) with respect to the microscopic lesions in liver, kidney, spleen, heart, brain, and lung, as well as the distribution of immunolabeling for YF virus antigen, and the flaviviral load in the liver. Of 43 titi monkeys examined, 18 (42%) were positive for yellow fever virus (YFV) by immunohistochemistry or reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Affected livers had consistent marked panlobular necrotizing hepatitis, lipidosis, and mild inflammation, with intense immunolabeling for YFV mainly in centrilobular hepatocytes (zone 1; P =.05). In the spleen, consistent findings were variable lymphoid depletion (10/11), lymphoid necrosis (lymphocytolysis; 4/11), and immunolabeling for YFV in histiocytic cells (3/16). The main finding in the kidney was multifocal acute necrosis of tubular epithelium (5/7) that was occasionally associated with intracytoplasmic immunolabeling for YFV (6/15). These data indicate that titi monkeys are susceptible to YFV infection, developing severe hepatic lesions and high viral loads, comparable to humans and Alouatta spp. Thus, Callicebus spp. may be reliable sentinels for YF surveillance. [ABSTRACT FROM AUTHOR]

A major outbreak of yellow fever (YF) occurred in Brazil during 2016-2018. Epizootics in New World nonhuman primates are sentinel events for YF virus circulation. However, genus-specific susceptibilities and suitability for YF surveillance remain poorly understood. We obtained and compared epidemiologic, histopathologic, immunohistochemical, and molecular results from 93 human and 1,752 primate cases submitted during the recent YF outbreak in Brazil (2017), with the support of the Brazilian National YF Surveillance Program. We detected heterogeneous YF-associated profiles among the various genera of primates we analyzed. Alouatta primates were the most reliable sentinel; Sapajus and Callicebus primates had higher viral loads but lower proportional mortality rates. Callithrix primates were the least sensitive, showing lower viral loads, lower proportional mortality rates, and no demonstrable YF virus antigen or extensive lesions in liver, despite detectable viral RNA. These differences in susceptibility, viral load, and mortality rates should be considered in strategic surveillance of epizootics and control measures for YF. [ABSTRACT FROM AUTHOR]

Cetacean morbillivirus (CeMV; Paramyxoviridae) is the most significant pathogen of cetaceans worldwide. The novel "multi-host" Guiana dolphin (Sotalia guianensis ; GD)-CeMV strain is reported in South American waters and infects Guiana dolphins and southern right whales (Eubalaena australis). This study aimed to describe the pathologic findings, GD-CeMV viral antigen distribution and detection by RT-PCR (reverse transcriptase polymerase chain reaction), and infectious comorbidities in 29 Guiana dolphins that succumbed during an unusual mass-mortality event in Rio de Janeiro state, Brazil, between November 2017 and March 2018. The main gross findings were lack of ingesta, pulmonary edema, ascites, icterus, hepatic lipidosis, multicentric lymphadenomegaly, as well as pneumonia, polyserositis, and multiorgan vasculitis caused by Halocercus brasiliensis. Microscopically, the primary lesions were bronchointerstitial pneumonia and multicentric lymphoid depletion. The severity and extent of the lesions paralleled the distribution and intensity of morbilliviral antigen. For the first time in cetaceans, morbilliviral antigen was detected in salivary gland, optic nerve, heart, diaphragm, parietal and visceral epithelium of glomeruli, vulva, and thyroid gland. Viral antigen within circulating leukocytes suggested this as a mechanism of dissemination within the host. Comorbidities included disseminated toxoplasmosis, mycosis, ciliated protozoosis, and bacterial disease including brucellosis. These results provide strong evidence for GD-CeMV as the main cause of this unusual mass-mortality event. [ABSTRACT FROM AUTHOR]

Aims: The clinical spectrum of yellow fever (YF) ranges from asymptomatic to fulminant hepatitis. During the sylvatic YF epidemic in the metropolitan area of São Paulo, Brazil in 2018, seven orthotopic liver transplantations (OLTs) were performed in our institution to treat fulminant YF hepatitis. Three patients recovered, while four patients died following OLT. The autopsy findings of all these cases are presented herein as the first description of YF in transplanted patients. Methods and results: All patients were men, aged 16–40 years, without vaccination to YF virus (YFV). All organs were examined, with tissue sampling for histopathological analysis. Detection of YF virus antigens (YFV Ag) was performed with two primary antibodies (mouse polyclonal anti‐YFV antibody directed to wild strain and a goat anti‐YF virus antibody), and RT–PCR assays were utilised to detect YFV‐RNA. All the cases depicted typical findings of YF hepatitis in the engrafted liver. The main extrahepatic findings were cerebral oedema, pulmonary haemorrhage, pneumonia, acute tubular necrosis and ischaemic/reperfusion pancreatitis. Of the four cases, the YVF Ag was detected in the heart in one case, liver and testis in three cases, and the kidney and spleen in all four cases. All four cases had YF virus RNA detected by RT–PCR in the liver and in other organs. Conclusions: Infection of the engrafted liver and other organs by YFV, possibly combined with major ischaemic systemic lesions, may have led to the death of four of the seven patients undergoing OLT. [ABSTRACT FROM AUTHOR]

Cetacean morbillivirus (CeMV) is a major natural cause of morbidity and mortality in cetaceans worldwide and results in epidemic and endemic fatalities. The pathogenesis of CeMV has not been fully elucidated, and questions remain regarding tissue tropism and the mechanisms of immunosuppression. We compared the histopathologic and viral immunohistochemical features in molecularly confirmed CeMV-infected Guiana dolphins (Sotalia guianensis) from the Southwestern Atlantic (Brazil) and striped dolphins (Stenella coeruleoalba) and bottlenose dolphins (Tursiops truncatus) from the Northeast-Central Atlantic (Canary Islands, Spain) and the Western Mediterranean Sea (Italy). Major emphasis was placed on the central nervous system (CNS), including neuroanatomical distribution of lesions, and the lymphoid system and lung were also examined. Eleven Guiana dolphins, 13 striped dolphins, and 3 bottlenose dolphins were selected by defined criteria. CeMV infections showed a remarkable neurotropism in striped dolphins and bottlenose dolphins, while this was a rare feature in CeMV-infected Guiana dolphins. Neuroanatomical distribution of lesions in dolphins stranded in the Canary Islands revealed a consistent involvement of the cerebrum, thalamus, and cerebellum, followed by caudal brainstem and spinal cord. In most cases, Guiana dolphins had more severe lung lesions. The lymphoid system was involved in all three species, with consistent lymphoid depletion. Multinucleate giant cells/syncytia and characteristic viral inclusion bodies were variably observed in these organs. Overall, there was widespread lymphohistiocytic, epithelial, and neuronal/neuroglial viral antigen immunolabeling with some individual, host species, and CeMV strain differences. Preexisting and opportunistic infections were common, particularly endoparasitism, followed by bacterial, fungal, and viral infections. These results contribute to understanding CeMV infections in susceptible cetacean hosts in relation to factors such as CeMV strains and geographic locations, thereby establishing the basis for future neuro- and immunopathological comparative investigations. [ABSTRACT FROM AUTHOR]

Abstract: We report the pathological, immunohistochemical, and molecular features of fatal acute systemic toxoplasmosis in an adult, female, free‐living southern muriqui (Brachyteles arachnoides) from São Paulo state, Brazil. PCR‐RFLP genotyping analysis identified the #21 genotype of Toxoplasma gondii. This represents the first report of acute toxoplasmosis involving this genotype in humans and animals. [ABSTRACT FROM AUTHOR]