Globoside and the mucosal pH mediate parvovirus B19 entry through the epithelial barrier.

Parvovirus B19 (B19V) is transmitted primarily via the respiratory route, however, the mechanism involved remains unknown. B19V targets a restricted receptor expressed in erythroid progenitor cells in the bone marrow. However, B19V shifts the receptor under acidic conditions and targets the widely expressed globoside. The pH-dependent interaction with globoside may allow virus entry through the naturally acidic nasal mucosa. To test this hypothesis, MDCK II cells and well-differentiated human airway epithelial cell (hAEC) cultures were grown on porous membranes and used as models to study the interaction of B19V with the epithelial barrier. Globoside expression was detected in polarized MDCK II cells and the ciliated cell population of well-differentiated hAEC cultures. Under the acidic conditions of the nasal mucosa, virus attachment and transcytosis occurred without productive infection. Neither virus attachment nor transcytosis was observed under neutral pH conditions or in globoside knockout cells, demonstrating the concerted role of globoside and acidic pH in the transcellular transport of B19V. Globoside-dependent virus uptake involved VP2 and occurred by a clathrin-independent pathway that is cholesterol and dynamin-dependent. This study provides mechanistic insight into the transmission of B19V through the respiratory route and reveals novel vulnerability factors of the epithelial barrier to viruses.

Human parvovirus B19 interacts with globoside under acidic conditions as an essential step in endocytic trafficking.

The glycosphingolipid (GSL) globoside (Gb4) is essential for parvovirus B19 (B19V) infection. Historically considered the cellular receptor of B19V, the role of Gb4 and its interaction with B19V are controversial. In this study, we applied artificial viral particles, genetically modified cells, and specific competitors to address the interplay between the virus and the GSL. Our findings demonstrate that Gb4 is not involved in the binding or internalization process of the virus into permissive erythroid cells, a function that corresponds to the VP1u cognate receptor. However, Gb4 is essential at a post-internalization step before the delivery of the single-stranded viral DNA into the nucleus. In susceptible erythroid Gb4 knockout cells, incoming viruses were arrested in the endosomal compartment, showing no cytoplasmic spreading of capsids as observed in Gb4-expressing cells. Hemagglutination and binding assays revealed that pH acts as a switch to modulate the affinity between the virus and the GSL. Capsids interact with Gb4 exclusively under acidic conditions and dissociate at neutral pH. Inducing a specific Gb4-mediated attachment to permissive erythroid cells by acidification of the extracellular environment led to a non-infectious uptake of the virus, indicating that low pH-mediated binding to the GSL initiates active membrane processes resulting in vesicle formation. In summary, this study provides mechanistic insight into the interaction of B19V with Gb4. The strict pH-dependent binding to the ubiquitously expressed GSL prevents the redirection of the virus to nonpermissive tissues while promoting the interaction in acidic intracellular compartments as an essential step in infectious endocytic trafficking.

Herpes simplex virus co-infection facilitates rolling circle replication of the adeno-associated virus genome.

Adeno-associated virus (AAV) genome replication only occurs in the presence of a co-infecting helper virus such as adenovirus type 5 (AdV5) or herpes simplex virus type 1 (HSV-1). AdV5-supported replication of the AAV genome has been described to occur in a strand-displacement rolling hairpin replication (RHR) mechanism initiated at the AAV 3' inverted terminal repeat (ITR) end. It has been assumed that the same mechanism applies to HSV-1-supported AAV genome replication. Using Southern analysis and nanopore sequencing as a novel, high-throughput approach to study viral genome replication we demonstrate the formation of double-stranded head-to-tail concatemers of AAV genomes in the presence of HSV-1, thus providing evidence for an unequivocal rolling circle replication (RCR) mechanism. This stands in contrast to the textbook model of AAV genome replication when HSV-1 is the helper virus.

Impact of the isoelectric point of model parvoviruses on viral retention in anion-exchange chromatography.

Anion-exchange chromatography (AEX) is used in the downstream purification of monoclonal antibodies to remove impurities and potential viral contamination based on electrostatic interactions. Although the isoelectric point (pI) of viruses is considered a key factor predicting the virus adsorption to the resin, the precise molecular mechanisms involved remain unclear. To address this question, we compared structurally homologous parvoviruses that only differ in their surface charge distribution. A single charged amino acid substitution on the capsid surface of minute virus of mice (MVM) provoked an increased apparent pI (pIapp ) 6.2 compared to wild-type MVM (pIapp = 4.5), as determined by chromatofocusing. Despite their radically different pIapp , both viruses displayed the same interaction profile in Mono Q AEX at different pH conditions. In contrast, the closely related canine parvovirus (pIapp = 5.3) displayed a significantly different interaction at pH 5. The detailed structural analysis of the intricate three-dimensional structure of the capsids suggests that the charge distribution is critical, and more relevant than the pI, in controlling the interaction of a virus with the chromatographic resin. This study contributes to a better understanding of the molecular mechanisms governing virus clearance by AEX, which is crucial to enable robust process design and maximize safety.

Globoside Is Dispensable for Parvovirus B19 Entry but Essential at a Postentry Step for Productive Infection.

Globoside (Gb4) is considered the primary receptor of parvovirus B19 (B19V); however, its expression does not correlate well with the attachment and restricted tropism of the virus. The N terminus of VP1 (VP1u) of B19V interacts with an as-yet-unknown receptor required for virus internalization. In contrast to Gb4, the VP1u cognate receptor is expressed exclusively in cells that B19V can internalize. With the aim of clarifying the role of Gb4 as a B19V receptor, we knocked out the gene B3GalNT1 coding for the enzyme globoside synthase in UT7/Epo cells. Consequently, B3GalNT1 transcripts and Gb4 became undetectable in the knockout (KO) cells without affecting cell viability and proliferation. Unexpectedly, virus attachment, internalization, and nuclear targeting were not disturbed in the KO cells. However, NS1 transcription failed, and consequently, genome replication and capsid protein expression were abrogated. The block could be circumvented by transfection with a B19V infectious clone, indicating that Gb4 is not required after the generation of viral double-stranded DNA with resolved inverted terminal repeats. While in wild-type (WT) cells, occupation of the VP1u cognate receptor with recombinant VP1u disturbed virus binding and blocked the infection, antibodies against Gb4 had no significant effect. In a mixed population of WT and KO cells, B19V selectively infected WT cells. This study demonstrates that Gb4 does not have the expected receptor function, as it is dispensable for virus entry; however, it is essential for productive infection, explaining the resistance of the rare individuals lacking Gb4 to B19V infection.IMPORTANCE Globoside has long been considered the primary receptor of B19V. However, its expression does not correlate well with B19V binding and uptake and cannot explain the pathogenesis or the remarkable narrow tissue tropism of the virus. By using a knockout cell line, we demonstrate that globoside does not have the expected function as a cell surface receptor required for B19V entry, but it has an essential role at a postentry step for productive infection. This finding explains the natural resistance to infection associated with individuals lacking globoside, contributes to a better understanding of B19V restricted tropism, and offers novel strategies for the development of antiviral therapies.

Comparison of the efficacy of 2 sedative protocols in pediatric dogs undergoing brainstem auditory-evoked response testing.

This study compared the quality of sedation with dexmedetomidine or alfaxalone during brainstem auditory-evoked response (BAER) tests in 6- to 17-week-old dogs. This was a prospective, randomized clinical study involving 19 client-owned pediatric dogs of breeds with reported congenital deafness. Group A (GA) received alfaxalone, 2 mg/kg body weight (BW) (n = 9) and group D (GD) dexmedetomidine, 0.005 mg/kg BW, and postprocedure antagonism with atipamezole (n = 10) intramuscularly. Time from injection to sedation, duration of sedation, sedation scores, need for re-dosing, rectal temperature, pulse and respiratory rate were recorded at baseline, before and after the BAER test, and once recovered from sedation. Pulse rate was significantly lower in GD (P = 0.004) and the number of re-dosing was significantly higher in GA (P = 0.011). Both sedation protocols allowed good quality BAER test recordings in pediatric dogs. Sedation with dexmedetomidine required less re-dosing, whereas alfaxalone maintained more physiological pulse rates.

Comparaison de l'efficacité de 2 protocoles de sédation chez des chiens pédiatriques soumis à un test potentiel évoqué auditif. L'étude vise à comparer deux protocoles de sédation à base de la dexmédétomidine et de l'alfaxalone pour la réalisation de test de potentiels évoqués auditifs (PEA) chez les chiens âgés de 6 à 17 semaines. Il s'agit d'une étude clinique prospective, randomisée, incluant 19 chiens pédiatriques de propriétaire, appartenant à des races prédisposées à la surdité congénitale. Les groupe A (GA) a reçu de l'alfaxalone (2 mg/kg) (n = 9), ceux du groupe D (GD) de la dexmédétomidine (0,005 mg/kg) (n = 10), en intramusculaire. Ont été relevés : temps d'action, durée de sédation, scores de sédation, nombre de doses, température, pouls et fréquence respiratoire; au repos, avant et après le test PEA. Des différences statistiquement significatives ont été trouvées dans la fréquence du pouls, étant plus bas pour GD (P = 0,004) alors que le nombre de doses utilisées, étant supérieurs parmi GA (P = 0,011). Trois chiens avaient une surdité unilatérale. Les deux protocoles de sédation ont permis des enregistrements de bonne qualité. La sédation avec la dexmédétomidine a nécessité moins de redosage; cependant, l'alfaxalone induit un pouls cardiaque plus proche des valeurs physiologiques chez les jeunes chiens testés.(Traduit par les auteurs).

Constrictive myelopathy secondary to caudal articular vertebral process dysplasia in West Highland white terrier dogs.

Clinical signs, imaging findings and long-term follow-up of 3 West Highland white terrier dogs with constrictive myelopathy secondary to caudal articular vertebral process dysplasia are described. Clinical signs were consistent with an acute or chronic T3-L3 myelopathy in all dogs. Diagnostic imaging revealed hypoplasia or aplasia of the caudal articular vertebral processes, extradural compressive myelographic pattern (hourglass-like pattern) with a reduced diameter of the spinal cord, and focal thickening of extradural soft tissues. Medical treatment initially improved the clinical signs in 2 dogs; however, mild proprioceptive deficits remained in all cases. Key clinical message: Constrictive myelopathy secondary to caudal articular vertebral process dysplasia in West Highland white terrier dogs should be considered as a differential diagnosis of an acute or chronic T3-L3 myelopathy in this breed.

Myélopathie constrictive secondaire à une dysplasie du processus articulaire caudal vertébral chez des chiens terriers West Highland white. Les signes cliniques, les trouvailles en imagerie et le suivi à longterme de trois chiens West Highland white avec myélopathie constrictive secondaire à une dysplasie du processus articulaire caudal vertébral sont décrits. Les signes cliniques étaient compatibles avec une myélopathie aiguë ou chronique au niveau T3­L3 chez tous les chiens. L'imagerie diagnostique a révélé une hypoplasie ou une aplasie des processus articulaires caudaux vertébraux, un patron myélographique de compression extra-dural (patron en sablier) avec un diamètre réduit de la moëlle épinière, et épaississement focal des tissus mous extra-duraux. Un traitement médical permis une amélioration des signes cliniques chez deux des chiens; toutefois, des déficits légers de proprioception ont persisté dans tous les cas.Message clinique clé:Une myélopathie constrictive secondaire à une dysplasie du processus articulaire caudal vertébral chez des chiens terriers West Highland white devrait être considérée comme un diagnostic différentiel d'une myélopathie aiguë ou chronique de T3­L3 chez cette race.(Traduit par Dr Serge Messier).

Late Maturation Steps Preceding Selective Nuclear Export and Egress of Progeny Parvovirus.

UNLABELLED: Although the mechanism is not well understood, growing evidence indicates that the nonenveloped parvovirus minute virus of mice (MVM) may actively egress before passive release through cell lysis. We have dissected the late maturation steps of the intranuclear progeny with the aims of confirming the existence of active prelytic egress and identifying critical capsid rearrangements required to initiate the process. By performing anion-exchange chromatography (AEX), we separated intranuclear progeny particles by their net surface charges. Apart from empty capsids (EC), two distinct populations of full capsids (FC) arose in the nuclei of infected cells. The earliest population of FC to appear was infectious but, like EC, could not be actively exported from the nucleus. Further maturation of this early population, involving the phosphorylation of surface residues, gave rise to a second, late population with nuclear export potential. While capsid surface phosphorylation was strictly associated with nuclear export capacity, mutational analysis revealed that the phosphoserine-rich N terminus of VP2 (N-VP2) was dispensable, although it contributed to passive release. The reverse situation was observed for the incoming particles, which were dephosphorylated in the endosomes. Our results confirm the existence of active prelytic egress and reveal a late phosphorylation event occurring in the nucleus as a selective factor for initiating the process. IMPORTANCE: In general, the process of egress of enveloped viruses is active and involves host cell membranes. However, the release of nonenveloped viruses seems to rely more on cell lysis. At least for some nonenveloped viruses, an active process before passive release by cell lysis has been reported, although the underlying mechanism remains poorly understood. By using the nonenveloped model parvovirus minute virus of mice, we could confirm the existence of an active process of nuclear export and further characterize the associated capsid maturation steps. Following DNA packaging in the nucleus, capsids required further modifications, involving the phosphorylation of surface residues, to acquire nuclear export potential. Inversely, those surface residues were dephosphorylated on entering capsids. These spatially controlled phosphorylation-dephosphorylation events concurred with the nuclear export-import potential required to complete the infectious cycle.

Comparison of the brainstem auditory evoked responses during sevoflurane or alfaxalone anaesthesia in adult cats.

OBJECTIVE: To compare the effects of general anaesthesia using sevoflurane or alfaxalone on the brainstem auditory evoked response (BAER) test in adult healthy cats. STUDY DESIGN: Prospective, clinical, 'blinded', crossover study. ANIMALS: Ten feral adult healthy cats. METHODS: Premedication consisted of dexmedetomidine (0.01 mg kg-1) intramuscularly (IM). The first general anaesthesia was induced and maintained with sevoflurane (treatment S) for physical examination, BAER test, complete blood tests, thoracic radiographs and abdominal ultrasound. The second general anaesthesia was induced with alfaxalone (treatment A) IM (2 mg kg-1) and maintained with alfaxalone (10 mg kg-1 hour-1) for the BAER test, followed by neutering surgery. The BAER recordings were compared for differences in latencies, amplitudes and waveform morphology. Data were analysed using Student's t test and Wilcoxon rank test for paired samples for parametric and non-parametric data, respectively. Statistical significance was set at p < 0.05. RESULTS: General anaesthesia was uneventful; normal BAER comprising five peaks could be identified in both treatments. Mean ± SD latencies were 1.05 ± 0.09, 1.83 ± 0.11, 2.52 ± 0.19, 3.43 ± 0.17 and 4.39 ± 0.15 ms and 1.03 ± 0.04, 1.81 ± 0.73, 2.53 ± 0.15, 3.37 ± 0.13 and 4.33 ± 0.13 ms in treatments S and A, respectively. Median (interquartile range) amplitudes were 2.83 (0.67), 1.27 (0.41), 0.30 (0.40), 1.05 (0.82), 0.61 (0.38) microvolts and 2.84 (1.21), 1.49 (1.18), 0.26 (0.32), 0.91 (0.50) and 0.92 (0.64) microvolts in treatments S and A, respectively. There were no statistically significant differences in mean latencies or median amplitudes between both the anaesthetics. CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrates that there were no statistically significant differences between both the anaesthetics on the BAER test in adult healthy cats. Moreover, two possible anaesthetic protocols are described for cats undergoing this electrodiagnostic test.

Specific Targeting of Proerythroblasts and Erythroleukemic Cells by the VP1u Region of Parvovirus B19.

Viruses are evolutionarily developed cell-entering nanomachines, which are frequently used as gene or drug delivery systems. Parvovirus B19 (B19V) shows a remarkably restricted tropism for erythropoietin-dependent erythroid differentiation stages, and thus this virus provides an opportunity to deliver cargo to these intermediate differentiated cells. Here we report the construction of a delivery system from B19V subunits that maintains the highly selective cell-entry of the native virus and offers versatile cargo transport. To obtain this specific carrier, we conjugated the cell-targeting VP1u region of B19V to NeutrAvidin as a loading platform for biotinylated cargos. The VP1u-NeutrAvidin conjugate delivered fluorophores, DNA, and toxic payloads specifically to erythroid cells around the proerythroblast differentiation stage, including erythroleukemic cells. The VP1u-NeutrAvidin represents a unique cell surface marker which exclusively detects intermediate erythroid differentiation stages. Furthermore, the cell-entering property of this viral-based targeting system offers opportunities for erythroid-specific drug delivery or gene therapy.

Parvovirus B19 uptake is a highly selective process controlled by VP1u, a novel determinant of viral tropism.

The VP1 unique region (VP1u) of human parvovirus B19 (B19V) is the immunodominant part of the viral capsid. Originally inaccessible, the VP1u becomes exposed upon primary attachment to the globoside receptor. To study the function of the exposed VP1u in B19V uptake, we expressed this region as a recombinant protein. Here, we report that purified recombinant VP1u binds and is internalized in UT7/Epo cells. By means of truncations and specific antibodies, we identified the most N-terminal amino acid residues of VP1u as the essential region for binding and internalization. Furthermore, the recombinant VP1u was able to block B19V uptake, suggesting that the protein and the virus undertake the same internalization pathway. Assays with different erythroid and nonerythroid cell lines showed that the N-terminal VP1u binding was restricted to a few cell lines of the erythroid lineage, which were also the only cells that allowed B19V internalization and infection. These results together indicate that the N-terminal region of VP1u is responsible for the internalization of the virus and that the interacting receptor is restricted to B19V-susceptible cells. The highly selective uptake mechanism represents a novel determinant of the tropism and pathogenesis of B19V.

Clinical signs, causes, and outcome of central cord syndrome in 22 cats.

OBJECTIVE: To describe the signalment, clinical findings, presumptive or definitive diagnosis, and outcome in cats with central cord syndrome (CCS). ANIMALS: 22 cats. CLINICAL PRESENTATION: Cats evaluated for CCS at 7 referral hospitals between 2017 and 2021 were included. Information retrieved from medical records included signalment, physical and neurological examination findings, diagnostic investigations, definitive or presumptive diagnosis, treatment, and follow-up. RESULTS: Median age at presentation was 9 years. Two neuroanatomical localizations were associated with CCS: C1-C5 spinal cord segments in 17 (77.3%) cats and C6-T2 spinal cord segments in 5 (22.7%) cats. Neuroanatomical localization did not correlate with lesion location on MRI in 8 (36.3%) cats. The most common lesion location within the vertebral column was over the C2 and C4 vertebral bodies in 6 (27.2%) and 5 (22.7%) cats, respectively. Peracute clinical signs were observed in 11 (50%) cats, acute in 1 (4.5%), subacute in 4 (18%), and chronic and progressive signs were seen in 6 (40.9%) cats. The most common peracute condition was ischemic myelopathy in 8 (36.3%) cats, whereas neoplasia was the most frequently identified chronic etiology occurring in 5 (22.7%) cats. Outcome was poor in 13 (59%) cats, consisting of 4 of 11 (36.6%) of the peracute cases, 3 of 4 (75%) of the subacute cases, and 6 of 6 of the chronic cases. CLINICAL RELEVANCE: Central cord syndrome can occur in cats with lesions in the C1-C5 and C6-T2 spinal cord segments. Multiple etiologies can cause CCS, most commonly, ischemic myelopathy and neoplasia. Prognosis depends on the etiology and onset of clinical signs.

Characterization of the early steps of human parvovirus B19 infection.

The early steps of human parvovirus B19 (B19V) infection were investigated in UT7/Epo cells. B19V and its receptor globoside (Gb4Cer) associate with lipid rafts, predominantly of the noncaveolar type. Pharmacological disruption of the lipid rafts inhibited infection when the drug was added prior to virus attachment but not after virus uptake. B19V is internalized by clathrin-dependent endocytosis and spreads rapidly throughout the endocytic pathway, reaching the lysosomal compartment within minutes, where a substantial proportion is degraded. B19V did not permeabilize the endocytic vesicles, indicating a mechanism of endosomal escape without apparent membrane damage. Bafilomycin A(1) (BafA1) and NH(4)Cl, which raise endosomal pH, blocked the infection by preventing endosomal escape, resulting in a massive accumulation of capsids in the lysosomes. In contrast, in the presence of chloroquine (CQ), the transfer of incoming viruses from late endosomes to lysosomes was prevented; the viral DNA was not degraded; and the infection was boosted. In contrast to the findings for untreated or BafA1-treated cells, the viral DNA was progressively associated with the nucleus in CQ-treated cells, reaching a plateau by 3 h postinternalization, a time coinciding with the initiation of viral transcription. At this time, more than half of the total intracellular viral DNA was associated with the nucleus; however, the capsids remained extranuclear. Our studies provide the first insight into the early steps of B19V infection and reveal mechanisms involved in virus uptake, endocytic trafficking, and nuclear penetration.

Magnetic spheres as foreign body into the bladder.

INTRODUCTION: A great variety of foreign bodies in the lower urinary tract have been described; many of them are self-inflicted by the patient with masturbatory purposes. Depending on the nature of the foreign body the diagnostic and management might be challenging. AIMS: We report a case of an unusual magnetic self-inserted foreign body into the bladder for autoerotism and briefly discuss the diagnostic and therapeutic implications in this challenging situation. METHODS: We describe all the steps we have used to adequately diagnose the problem, describe the foreign body and treatments for the patient. Related articles were found by utilizing the PubMed database and are summarized in this study. RESULTS: The management approach must be planned according to the nature of the foreign body and should minimize bladder and urethral trauma. However, most of cases can be managed endoscopically. CONCLUSION: Removal of magnetic foreign body may be quite challenging, requiring high-level surgical skills and minimally invasive techniques resulting in fast recovery and low complication rate.

Twenty-five milligrams of clomiphene citrate presents positive effect on treatment of male testosterone deficiency - a prospective study.

INTRODUCTION: Male testosterone deficiency is associated with bad sexual function and quality of life (QoL). The aim of this study was to determine whether a daily dose of 25 mg clomiphene citrate (CC) is effective in stimulating the endogenous testosterone production pathway and to address the applicability of this medication as a therapeutic option for symptomatic hypogonadism. MATERIALS AND METHODS: This was a prospective study. Men with low sexual desire and testosterone levels (T) below 400 ng/dL were selected to receive CC. Blood samples were obtained to determine baseline measurements of serum T, estradiol, LH, lipid profile and fasting plasma glucose. Each patient was treated with a daily dose of 25 mg CC for at least 3 months. Patients were asked if they experienced any side effects related to the use of CC and if they experienced any improvement in their sexual profile. Paired samples T-test was utilized to analyze responses to therapy. RESULTS: Our cohort consisted of 125 men with hypogonadism and low libido. Mean age was 62 years (± 11.1 years). Serum T levels ranged from 309 ng/dL (baseline, mean value) to 642 ng/dL (3 months after CC initiation, mean value) (p < 0.001). Serum cholesterol levels ranged from 197 to 186 mg/dL (p = 0.003). There were no statistically significant differences when comparing pre and post-treatment HDL-Cholesterol, triglycerides, fasting plasma glucose and prolactin. All men reported improvements in the post-treatment QoL scores. No serious adverse events were recorded. CONCLUSIONS: The CC was effective in stimulating the endogenous production of testosterone. A lower level of total cholesterol was verified after three months of treatment. This medication should be considered as a therapeutic option for some patients with symptomatic male testosterone deficiency.

Long-term follow-up of penile curvature correction utilizing autologous albugineal crural graft.

PURPOSE: Peyronie 's disease is an acquired connective tissue disorder of the penile tunica albuginea with fibrosis and inflammation. The disease produces palpable plaques, penile curvature and pain during erections. Usually it results in impairment of the quality of life. Our objective is to review the long-term results of the albugineal grafting harvested from the penile crura for the treatment of severe penile curvature. MATERIALS AND METHODS: Thirty-three patients with Peyronie 's disease were submitted to a grafting with tunica albuginea from the penile crura for the correction of penile curvature. The results were evaluated after 6 months of the procedure. Variables studied were overall satisfaction with the procedure, correction of the penile curvature, erectile capacity, penile shortening and the presence of surgical complications. RESULTS: Mean follow-up after surgery was 41 months. Complete correction of the curvature was achieved in 30 patients (90%). The mean preoperative curvature was 91.8 degrees and median plaque length was 2 cm (ranged from 1 to 5 cm). Three patients (9%) experienced recurrence of the penile curvature and required a new procedure. In 30 men (90%) the procedure fulfilled their expectations and in 31 patients (93.9%) their opinions were that sexual partners were satisfied with the penile correction. Penile shortening or augmentation was referred in 6 (18.1%) and 1 (3%) patient, respectively. CONCLUSION: Our series demonstrated that grafting the albugineal defect after incision of the tunica albuginea with tunica from the crus for the correction of penile curvature is safe and results in satisfactory straight erections during along-term follow-up.

A Conserved Receptor-Binding Domain in the VP1u of Primate Erythroparvoviruses Determines the Marked Tropism for Erythroid Cells.

Parvovirus B19 (B19V) is a human pathogen with a marked tropism for erythroid progenitor cells (EPCs). The N-terminal of the VP1 unique region (VP1u) contains a receptor-binding domain (RBD), which mediates virus uptake through interaction with an as-yet-unknown receptor (VP1uR). Considering the central role of VP1uR in the virus tropism, we sought to investigate its expression profile in multiple cell types. To this end, we established a PP7 bacteriophage-VP1u bioconjugate, sharing the size and VP1u composition of native B19V capsids. The suitability of the PP7-VP1u construct as a specific and sensitive VP1uR expression marker was validated in competition assays with B19V and recombinant VP1u. VP1uR expression was exclusively detected in erythroid cells and cells reprogrammed towards the erythroid lineage. Sequence alignment and in silico protein structure prediction of the N-terminal of VP1u (N-VP1u) from B19V and other primate erythroparvoviruses (simian, rhesus, and pig-tailed) revealed a similar structure characterized by a fold of three or four α-helices. Functional studies with simian parvovirus confirmed the presence of a conserved RBD in the N-VP1u, mediating virus internalization into human erythroid cells. In summary, this study confirms the exclusive association of VP1uR expression with cells of the erythroid lineage. The presence of an analogous RBD in the VP1u from non-human primate erythroparvoviruses emphasizes their parallel evolutionary trait and zoonotic potential.