scholarly journals The Post-Acute Phase of SARS-CoV-2 Infection in Two Macaque Species Is Associated with Signs of Ongoing Virus Replication and Pathology in Pulmonary and Extrapulmonary Tissues

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1673 ◽  
Author(s):  
Kinga P. Böszörményi ◽  
Marieke A. Stammes ◽  
Zahra C. Fagrouch ◽  
Gwendoline Kiemenyi-Kayere ◽  
Henk Niphuis ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Virus Replication ◽  
Acute Phase ◽  
Messenger Rna ◽  
Viral Rna ◽  
Mesenteric Lymph Nodes ◽  
Tissue Samples ◽  
Positron Emission ◽  
Wide Range ◽  
Tracheobronchial Lymph Nodes

The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis). During the acute phase of infection, SARS-CoV-2 was shed via the nose and throat, and viral RNA was occasionally detected in feces. This phase coincided with a transient change in systemic immune activation. Even after the alleged resolution of the infection, computed tomography (CT) and positron emission tomography (PET)-CT revealed pulmonary lesions and activated tracheobronchial lymph nodes in all animals. Post-mortem histological examination of the lung tissue revealed mostly marginal or resolving minimal lesions that were indicative of SARS-CoV-2 infection. Evidence for SARS-CoV-2-induced histopathology was also found in extrapulmonary tissue samples, such as conjunctiva, cervical, and mesenteric lymph nodes. However, 5–6 weeks after SARS-CoV-2 exposure, upon necropsy, viral RNA was still detectable in a wide range of tissue samples in 50% of the macaques and included amongst others the heart, the respiratory tract and surrounding lymph nodes, salivary gland, and conjunctiva. Subgenomic messenger RNA was detected in the lungs and tracheobronchial lymph nodes, indicative of ongoing virus replication during the post-acute phase. These results could be relevant for understanding the long-term consequences of COVID-19 in humans.

Mycobacterium avium subsp. avium in Lymph Nodes and Diaphragms of Pigs from One Infected Herd in the Czech Republic

2014 ◽  
Vol 77 (1) ◽  
pp. 141-144 ◽  
Author(s):  
PETR KRIZ ◽  
MARIJA KAEVSKA ◽  
IVA SLANA ◽  
IVA BARTEJSOVA ◽  
IVO PAVLIK
Keyword(s):  
Lymph Nodes ◽  
Mycobacterium Avium ◽  
Mycobacterium Avium Subsp ◽  
Mesenteric Lymph Nodes ◽  
Tissue Samples ◽  
The Czech Republic ◽  
Mesenteric Lymph ◽  
Qpcr Method ◽  
Pig Carcasses ◽  
Slaughtered Pigs

This study was performed on 40 finished pigs from one herd naturally infected with Mycobacterium avium subsp. avium. The aim was to investigate the presence and amount of M. a. avium in samples of lymph nodes and diaphragm tissues collected during routine postmortem inspection using the triplex quantitative real time PCR (qPCR) method. We collected, in total, 107 samples: various lymph nodes affected by gross tuberculosis (TB)–like lesions from 17 pig carcasses, as well as samples of head and mesenteric lymph nodes from 23 carcasses without TB-like lesions. Samples of diaphragm tissues were collected from all carcasses. M. a. avium was detected in one or more tissue samples collected from half of the slaughtered pigs tested. Samples of diaphragm tissues of three pigs with detected TB-like lesions contained M. a. avium (102 to 103 cells per g of sample); the organism was not detected in diaphragm tissues from pigs without TB-like lesions. The qPCR method may be useful for quantification of M. a. avium in pigs for the purposes of foodborne risk assessment.

scholarly journals A mixed infection of Mycobacterium avium subsp. paratuberculosis and M. a. hominissuis in one red deer (Cervus elaphus) studied by IS900 BstEII and IS1245 PvuII RFLP analyses: a case report

2008 ◽  
Vol 53 (No. 8) ◽  
pp. 445-451 ◽  
Author(s):  
M. Moravkova ◽  
I. Trcka ◽  
J. Lamka ◽  
I. Pavlik
Keyword(s):  
Lymph Nodes ◽  
Mycobacterium Avium ◽  
Cervus Elaphus ◽  
Mixed Infection ◽  
Red Deer ◽  
Chronic Diarrhoea ◽  
Mesenteric Lymph Nodes ◽  
Tissue Samples ◽  
Mesenteric Lymph ◽  
Rflp Type

A mixed infection with <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> (<i>MAP</i>) and <i>Mycobacterium avium</i> subsp. <i>hominissuis</i> (<i>MAH</i>) in one naturally infected red deer stag from a game park is described. The animal was euthanized because of symptoms of poor condition, weight loss and chronic diarrhoea. In spite of that, pathological lesions were observed only in the mesenteric lymph nodes, which were five to ten times enlarged with confluent caseous granulomas of 1 to 10 mm in size. Mycobacteria were isolated from all studied samples: a mixed infection of <i>MAP</i> and <i>MAH</i> was confirmed by multiplex PCR for the detection of IS <i>900</i>, IS<i>901</i>1, IS<i>1245</i> and <i>dnaJ</i>. MAP</i> of the identical IS<i>900</i> <i>BstE</i>II RFLP type C1 was isolated from all tissue samples and faeces. <i>MAH</i> isolates were detected in six examined tissue samples, including three mesenteric lymph nodes with caseous granulomas. Only minor differences in the band numbers and position of four different IS<i>1245</i> <i>Pvu</i>II RFLP patterns of <i>MAH</i> isolates were found. It follows from these results that red deer may potentially be infected with <i>MAH</i>, when a <i>MAP</i> infection is under way.

scholarly journals The Relationship between Simian Immunodeficiency Virus RNA Levels and the mRNA Levels of Alpha/Beta Interferons (IFN-α/β) and IFN-α/β-Inducible Mx in Lymphoid Tissues of Rhesus Macaques during Acute and Chronic Infection

2002 ◽  
Vol 76 (16) ◽  
pp. 8433-8445 ◽  
Author(s):  
Kristina Abel ◽  
Michelle J. Alegria-Hartman ◽  
Kristina Rothaeusler ◽  
Marta Marthas ◽  
Christopher J. Miller
Keyword(s):  
Virus Replication ◽  
Acute Phase ◽  
Rhesus Macaques ◽  
Viral Rna ◽  
Lymphoid Tissues ◽  
Mrna Levels ◽  
Immunodeficiency Virus ◽  
Siv Infection ◽  
Alpha Beta ◽  
Rna Levels

ABSTRACT To define the role of alpha/beta interferons (IFN-α/β) in simian immunodeficiency virus (SIV) infection, IFN-α and IFN-β mRNA levels and mRNA levels of Mx, an antiviral effector molecule, were determined in lymphoid tissues of rhesus macaques infected with pathogenic SIV. IFN-α/β responses were induced during the acute phase and persisted in various lymphoid tissues throughout the chronic phase of infection. IFN-α/β responses were most consistent in tissues with high viral RNA levels; thus, IFN-α/β responses were not generally associated with effective control of SIV replication. IFN-α/β responses were differentially regulated in different lymphoid tissues and at different stages of infection. The most consistent IFN-α/β responses in acute and chronic SIV infection were observed in peripheral lymph nodes. In the spleen, only a transient increase in IFN-α/β mRNA levels during acute SIV infection was observed. Further, IFN-α and IFN-β mRNA levels showed a tissue-specific expression pattern during the chronic, but not the acute, phase of infection. In the acute phase of infection, SIV RNA levels in lymphoid tissues of rhesus macaques correlated with mRNA levels of both IFN-α and IFN-β, whereas during chronic SIV infection only increased IFN-α mRNA levels correlated with the level of virus replication in the same tissues. In lymphoid tissues of all SIV-infected monkeys, higher viral RNA levels were associated with increased Mx mRNA levels. We found no evidence that monkeys with increased Mx mRNA levels in lymphoid tissues had enhanced control of virus replication. In fact, Mx mRNA levels were associated with high viral RNA levels in lymphoid tissues of chronically infected animals.

scholarly journals Enhancement of immunohistochemical detection of Salmonella in tissues of experimentally infected pigs

2015 ◽  
Vol 59 (3) ◽  
Author(s):  
J. Rieger ◽  
P. Janczyk ◽  
H. Hünigen ◽  
J. Plendl
Keyword(s):  
Lymph Nodes ◽  
Detection System ◽  
Intestinal Damage ◽  
Immunohistochemical Detection ◽  
Mesenteric Lymph Nodes ◽  
Tissue Samples ◽  
Serovar Typhimurium ◽  
Triton X ◽  
Foodborne Infections ◽  
Higher Sensitivity

<p><em>Salmonella</em> Typhimurium is one of the main pathogens compromising porcine and human health as well as food safety, because it is a prevailing source of foodborne infections due to contaminated pork. A prominent problem in the management of this bacteriosis is the number of subclinically infected carrier pigs. As very little is known concerning the mechanisms allowing <em>Salmonella</em> to persist in pigs, the objective of this study was to develop an immunohistochemical approach for the detection of salmonellae in tissue of pigs experimentally infected with <em>Salmonella</em> Typhimurium. Samples were obtained from a challenge trial in which piglets of the German Landrace were intragastrically infected with <em>Salmonella</em> enterica serovar Typhimurium DT104 (1.4-2.1x10<sup>10</sup> CFU). Piglets were sacrificed on days 2 and 28 post infection. Tissue samples of jejunum, ileum, colon, ileocecal mesenteric lymph nodes (<em>Lnn. ileocolici</em>), and tonsils (<em>Tonsilla veli palatini</em>) were fixed in Zamboni’s fixative and paraffin-embedded. Different immunohistochemical staining protocols were evaluated. <em>Salmonella</em> was detected in varying amounts in the tissues. Brown iron-containing pigments in the lymph nodes interfered with the identification of <em>Salmonella</em> if DAB was used as a staining reagent. Detergents like Triton X-100 or Saponin enhanced the sensitivity. It seems advisable not to use a detection system with brown staining for bacteria in an experimental setup involving intestinal damage including haemorrhage. The use of detergents appears to result in a higher sensitivity in the immunohistochemical detection of salmonellae.</p>

scholarly journals Chaperone-Assisted Protein Folding Is Critical for Yellow Fever Virus NS3/4A Cleavage and Replication

2016 ◽  
Vol 90 (6) ◽  
pp. 3212-3228 ◽  
Author(s):  
Leonia Bozzacco ◽  
Zhigang Yi ◽  
Ursula Andreo ◽  
Claire R. Conklin ◽  
Melody M. H. Li ◽  
...  
Keyword(s):  
Protein Folding ◽  
Yellow Fever ◽  
Virus Replication ◽  
Yellow Fever Virus ◽  
Rna Replication ◽  
Fever Virus ◽  
Viral Rna ◽  
Wild Type ◽  
Polyprotein Processing ◽  
Wide Range

ABSTRACTDNAJC14, a heat shock protein 40 (Hsp40) cochaperone, assists with Hsp70-mediated protein folding. Overexpressed DNAJC14 is targeted to sites of yellow fever virus (YFV) replication complex (RC) formation, where it interacts with viral nonstructural (NS) proteins and inhibits viral RNA replication. How RCs are assembled and the roles of chaperones in this coordinated process are largely unknown. We hypothesized that chaperones are diverted from their normal cellular protein quality control function to play similar roles during viral infection. Here, we show that DNAJC14 overexpression affects YFV polyprotein processing and alters RC assembly. We monitored YFV NS2A-5 polyprotein processing by the viral NS2B-3 protease in DNAJC14-overexpressing cells. Notably, DNAJC14 mutants that did not inhibit YFV replication had minimal effects on polyprotein processing, while overexpressed wild-type DNAJC14 affected the NS3/4A and NS4A/2K cleavage sites, resulting in altered NS3-to-NS3-4A ratios. This suggests that DNAJC14's folding activity normally modulates NS3/4A/2K cleavage events to liberate appropriate levels of NS3 and NS4A and promote RC formation. We introduced amino acid substitutions at the NS3/4A site to alter the levels of the NS3 and NS4A products and examined their effects on YFV replication. Residues with reduced cleavage efficiency did not support viral RNA replication, and only revertant viruses with a restored wild-type arginine or lysine residue at the NS3/4A site were obtained. We conclude that DNAJC14 inhibition of RC formation upon DNAJC14 overexpression is likely due to chaperone dysregulation and that YFV probably utilizes DNAJC14's cochaperone function to modulate processing at the NS3/4A site as a mechanism ensuring virus replication.IMPORTANCEFlaviviruses are single-stranded RNA viruses that cause a wide range of illnesses. Upon host cell entry, the viral genome is translated on endoplasmic reticulum (ER) membranes to produce a single polyprotein, which is cleaved by host and viral proteases to generate viral proteins required for genome replication and virion production. Several studies suggest a role for molecular chaperones during these processes. While the details of chaperone roles have been elusive, in this report we show that overexpression of the ER-resident cochaperone DNAJC14 affects YFV polyprotein processing at the NS3/4A site. This work reveals that DNAJC14 modulation of NS3/4A site processing is an important mechanism to ensure virus replication. Our work highlights the importance of finely regulating flavivirus polyprotein processing. In addition, it suggests future studies to address similarities and/or differences among flaviviruses and to interrogate the precise mechanisms employed for polyprotein processing, a critical step that can ultimately be targeted for novel drug development.

scholarly journals Quantitative Imaging Analysis of the Spatial Relationship between Antiretrovirals, RT-SHIV RNA, and Collagen in the Mesenteric Lymph Nodes of Nonhuman Primates

2021 ◽  
Author(s):  
Erin M.B. Scholz ◽  
Joseph N. Mwangi ◽  
Gabriela De la Cruz ◽  
Michael Nekorchuk ◽  
Chi Ngai Chan ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Nonhuman Primates ◽  
Quantitative Imaging ◽  
Viral Rna ◽  
Lymphoid Tissues ◽  
Imaging Analysis ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Tissue Area ◽  
Total Tissue

HIV persistence in tissue reservoirs is a major barrier to HIV cure. While antiretrovirals (ARVs) suppress viral replication, antiretroviral therapy (ART) interruption results in rapid rebound viremia that may originate from lymphoid tissues. To understand the relationship between anatomic distribution of ARV exposure and viral expression in lymph nodes, we performed mass spectrometry imaging (MSI) of 6 ARVs, RNAscope in situ hybridization for viral RNA, and immunohistochemistry of collagen in mesenteric lymph nodes from 8 uninfected and 10 reverse transcriptase-simian/human immunodeficiency virus (RT-SHIV) infected rhesus macaque nonhuman primates (NHPs) dosed to steady-state with combination ART. MATLAB-based quantitative imaging analysis was used to evaluate spatial and pharmacologic relationships between these ARVs, viral RNA (both vRNA+ cells and FDC-bound virions) and collagen deposition. Using MSI, 31% of mesenteric lymph node tissue area was not covered by any ARV. Additionally, 28% of FDC-trapped virions and 21% of infected cells were not exposed to any detected ARV. Of the 69% of tissue area that was covered by cumulative ART exposure, nearly 100% of concentrations were greater than in vitro IC50 values; however, 52% of total tissue coverage was from only one ARV, primarily maraviroc. Collagen covered ∼35% of tissue area, but did not influence ARV distribution heterogeneity. Our findings are consistent with our hypothesis that ARV distribution, in addition to total-tissue drug concentration, must be considered when evaluating viral persistence in lymph nodes and other reservoir tissues.

scholarly journals FDG Uptakes at Unilateral Axillary and Supraclavicular Lymph Nodes and Deltoid Muscle on [18F] FDG PET/CT After COVID-19 Vaccination: A Potential Pitfall for Metastatic Lymph Nodes in Colon Cancer Patient

2021 ◽  
Vol 5 (1) ◽  
pp. 72-76
Author(s):  
Jin Sol Choi ◽  
Se Hyung Kim
Keyword(s):  
Colon Cancer ◽  
Lymph Nodes ◽  
Deltoid Muscle ◽  
Left Shoulder ◽  
Contrast Enhanced Ct ◽  
Positron Emission ◽  
Supraclavicular Lymph Nodes ◽  
Pet Ct ◽  
Wide Range ◽  
Vectored Vaccine

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the ongoing global pandemic. It can manifest a wide range of complications depending upon the severity of infection and comorbidities of the patient. Vaccines are very important measure to provide protection against COVID-19. We report a case of 73-year-old female who underwent [<sup>18</sup>F]F-2-fluoro-2-deoxyd-glucose (FDG) positron emission tomography/computed tomography (PET/CT) and contrast-enhanced CT for staging of her rectosigmoid colon cancer and was found to have hypermetabolic uptakes in the deltoid muscle of the left shoulder and hypermetabolic left axillary and supraclavicular lymph nodes due to adenovirus vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca) administrated 18 days ago prior to PET/CT scan.

scholarly journals IgA production, coliforms analysis and intestinal mucosa morphology of piglets that received probiotics with viable or inactivated cells

2007 ◽  
Vol 27 (6) ◽  
pp. 241-245 ◽  
Author(s):  
Maria A. Martins Rodrigues ◽  
Deise A. de Oliveira Silva ◽  
Ernesto A. Taketomi ◽  
Francisco J. Hernandez-Blazquez
Keyword(s):  
Lymph Nodes ◽  
Lactobacillus Acidophilus ◽  
Serum Levels ◽  
Bifidobacterium Bifidum ◽  
Control Group ◽  
Mesenteric Lymph Nodes ◽  
Tissue Samples ◽  
Mesenteric Lymph ◽  
Health And Development ◽  
Iga Production

Two types of probiotics were used in piglets. One product is a mixed culture of viable Lactobacillus acidophilus, Enterococcus faecium e Bifidobacterium bifidum. The second product is composed of inactivated Lactobacillus acidophilus cells. The piglets received two weekly oral doses for 30 days while a control group did not receive probiotics. All piglets were euthanized at the 30th day of life and the mesenteric lymph nodes, the small intestine, and blood samples were collected. The tissue samples were studied by light microscopy and the blood serum was analyzed by ELISA method. The treatment with the probiotic with viable cells produced higher serum levels of IgA (P<0.05) and more IgA expressing cells were found in the mesenteric lymph nodes than observed in the inactivated cells treatment or control groups (P<0.05). Also, intestinal villi were longer, crypts were deeper (P<0.05) and fecal coliform count was lower than found in the inactivated product (P<0.05). These results suggest that viable probiotics are more efficient than inactivated probiotics to induce immunostimulation and intestinal modifications in piglets, thus improving their health and development.

scholarly journals Isolation of Mycobacterium avium subsp. paratuberculosis from mouflon in Bulgaria

2020 ◽  
Vol 9 (5-6) ◽  
pp. 665-670
Author(s):  
T. Savova ◽  
R. Petrova ◽  
V. Valcheva ◽  
M. Bonovska ◽  
H. Najdenski
Keyword(s):  
Lymph Nodes ◽  
Mycobacterium Avium ◽  
Intestinal Wall ◽  
Mesenteric Lymph Nodes ◽  
Tissue Samples ◽  
Diffuse Infiltration ◽  
Domestic Ruminants ◽  
Mesenteric Lymph ◽  
Faecal Samples ◽  
Depth Study

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of paratuberculosis (John’s disease) mainly in large and small domestic and wild ruminants, and suspected causative agent in human Crohn’s disease. In Bulgaria, paratuberculosis is still poorly researched in both groups of ruminants. We present results of the first in-depth study of mouflon, grown free in one hunting reserve in the Western region of the country. The aim was to prove the presence of MAP in diagnostic materials from regularly hunted or dead mouflon suspected for paratuberculosis. Small intestine and mesenteric lymph nodes (MLN) from 12 hunted and 4 dead mouflon and 10 faecal samples (Fc) were studied in the period of 2009–2013. Typical for paratuberculosis pathomorphological lesions were observed in four mouflon (of 16 examined). The intestinal wall was thickened, strongly folded and soft, with severe hyperemia. The MLN were enlarged, soft, with marbled appearance. The affected section of the ileum showed hyperplasia of the mucous corion and submucosa with diffuse infiltration of epithelioid cells. Lymphadenopathy with atrophy of T and B lymphocytes areas was observed in the mesenteric lymph nodes. For bacteriological isolation of MAP, the tissue and faecal samples were decontaminated with NALC-NaOH, cultured in Middlebrook 7H9 Broth and on Herrold’s medium. The Ziehl–Neelsen stained smears and isolates were examined microscopically for acid-fast bacteria. Presence of MAP was observed in tissue samples of 4 (25%) mouflon and in 2 (20%) faecal samples. The same samples were confirmed by the IS900 PCR for the presence of specific for MAP fragments with a commercial amplification kit. The cases of paratuberculosis found at different times in the free-living mouflon in our study prove that the disease exists in Bulgaria and highlight the need for more serious control of the disease among wild and domestic ruminants.

scholarly journals PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure

2020 ◽  
Author(s):  
Roslyn A. Taylor ◽  
Sixia Xiao ◽  
Ann M. Carias ◽  
Michael D. McRaven ◽  
Divya N. Thakkar ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Fluorescent Microscopy ◽  
Hiv Vaccines ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Mucosal Tissues ◽  
Positron Emission ◽  
Antibody Class ◽  
Photoactivatable Gfp

AbstractHIV vaccines have not been successful in clinical trials. Dimeric IgA (dIgA) is the most abundant antibody class in mucosal tissues, making dIgA a prime candidate for potential HIV vaccines. We coupled Positron Emission Tomography (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-GFP HIV (PA-GFP-BaL) and fluorescently labeled dIgA to determine how dIgA antibodies influence virus interaction with mucosal barriers and viral penetration in colorectal tissue. Our results show that HIV virions rapidly disseminate throughout the colon two hours after exposure. The presence of dIgA resulted in an increase in virions and penetration depth in the transverse colon. Moreover, virions were found in the mesenteric lymph nodes two hours after viral exposure, and the presence of dIgA led to an increase in virions in mesenteric lymph nodes. Taken together, these technologies enable in vivo and in situ visualization of antibody-virus interactions and detailed investigations of early events in HIV infection.

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