Coxsackievirus B4 Transplacental Infection Severely Disturbs Central Tolerogenic Mechanisms in the Fetal Thymus

Thymus plays a fundamental role in central tolerance establishment, especially during fetal life, through the generation of self-tolerant T cells. This process consists in T cells education by presenting them tissue-restricted autoantigens promiscuously expressed by thymic epithelial cells (TECs), thus preventing autoimmunity. Thymus infection by Coxsackievirus B (CV-B) during fetal life is supposed to disturb thymic functions and, hence, to be an inducing or accelerating factor in the genesis of autoimmunity. To further investigate this hypothesis, in our current study, we analyzed thymic expression of autoantigens, at the transcriptional and protein level, following in utero infection by CV-B4. mRNA expression levels of Igf2 and Myo7, major autoantigens of pancreas and heart, respectively, were analyzed in whole thymus and in enriched TECs together along with both transcription factors, Aire and Fezf2, involved in autoantigens expression in the thymus. Results show that in utero infection by CV-B4 induces a significant decrease in Igf2 and Myo7 expression at both mRNA and protein level in whole thymus and in enriched TECs as well. Moreover, a correlation between viral load and autoantigens expression can be observed in the whole thymus, indicating a direct effect of in utero infection by CV-B4 on autoantigens expression. Together, these results indicate that an in utero infection of the thymus by CV-B4 may interfere with self-tolerance establishment in TECs by decreasing autoantigen expression at both mRNA and protein level and thereby increase the risk of autoimmunity onset.

Chapter 7: TBE in special situations

TBE often takes a severe clinical course in immuno-suppressed patients. In transplant patients TBE usually takes a fatal course. TBE vaccination in immuno-suppressed patients can be non-effective TBE in pregnancy has rarely been reported; from recent cases there is no evidence of transplacental infection of the offspring. The alimentary route of infection of TBE is still common in some European countries resulting in a high clinical manifestation index. TBEV can be infectious in milk and milk products for up to 14 days under optimal environmental conditions. TBE is an important travel-related disease. Increasing numbers of non-endemic countries report imported cases. Imported TBE cases in non-endemic areas pose challenges regarding the diagnosis of TBE.

Current State of Knowledge about Transplacental Transmission of SARS-CoV-2 Infection

Background: To date, some cases of perinatal transmission of severe acute respiratory syndrome coronavirus-2 (SARS‐CoV‐2) have been reported. However, it is unanswered if these occurred via the trans-placental or the trans-cervical route or through environmental exposure. Methods: To address this question, we conducted this study to review the current state of knowledge about the transplacental transmission of COVID-19. Results: There are no known placental findings associated with the COVID-19 infection. The possibility of intrauterine infection has been based mainly on the detection of IgM in the neonatal blood. Real time-PCR tests on amniotic fluid, placenta, and cord blood are required to ascertain the possibility of intrauterine vertical transmission. Conclusion: There is currently no sufficient and convincing evidence about the transplacental transmission of SARS-COV-2 infection in pregnant mothers. However, the paucity of placental expression of ACE-2 involved in the cytoplasmic entry of SARS-CoV-2 may explain its relative insensitivity to transplacental infection.

Human Herpesviruses 6A and 6B in Reproductive Diseases

Human herpesviruses 6A (HHV-6A) and human herpesvirus 6B (HHV-6B)—collectively, HHV-6A/B—are recently-discovered but ancient human viruses. The vast majority of people acquire one or both viruses, typically very early in life, producing an ineradicable lifelong infection. The viruses have been linked to several neurological, pulmonary and hematological diseases. In early human history, the viruses on multiple occasions infected a germ cell, and integrated their DNA into a human chromosome. As a result, about 1% of humans are born with the full viral genome present in every cell, with uncertain consequences for health. HHV-6A may play a role in 43% of cases of primary unexplained infertility. Both the inherited and acquired viruses may occasionally trigger several of the factors that are important in the pathogenesis of preeclampsia. Transplacental infection occurs in 1-2% of pregnancies, with some evidence suggesting adverse health consequences for the child. While emerging knowledge about these viruses in reproductive diseases is not sufficient to suggest any changes in current practice, we write this review to indicate the need for further research that could prove practice-changing.

Transmissibility: To be or not to be

Appraising SARS-CoV-2 virus under the taxonomy category of coronaviridae family, which has been responsible for more than two million fatalities across the globe. It not only jeopardizes the normal life, but also potentiating the evolutionary progress towards a more lethal form. The lethal form, albeit is a bit virulent, is likely to predominate, thereby causing cumulative damage in any cluster that cannot even combat the wide spectrum of genetic variation. The impact on the vertical COVID-19 transmissibility of antenatal population is still sketchy about “nosocomial transmission” and the measures crude. The paper has reviewed the placental pathological findings of pregnant women afflicted with SARS-CoV-2 including the information, gathered from the subsequent stages of gestational outcomes. The possibility of the vertical transmission of SARS-CoV-2 due to the probable placental barrier damage caused by the severe maternal hypoxia, Homo sapiens (human) angiotensin-converting enzyme-2 (hACE2) influenced transplacental migration of SARS-CoV-2 in advanced gestational age, the plausible presence of RNAemia (detection of SARS-CoV-2 in the blood) in hematogenous route was reviewed in this paper. Nevertheless, the probability of susceptible intrauterine or perinatal infection of fetus does not conclusively decide as chances of involving placental coexpression of hACE2 and transmembrane protease, serine 2 in cytoplasmic entry of SARS-CoV-2 remains insignificant, exhibiting the probable relative insensitivity to transplacental infection. The present paper will provide an important insight about the wider understanding of the SARS-CoV-2 pathogenesis in the placenta that canvassed across all trimesters of pregnancy in response to the indiscriminate spread across globe at the time of therapeutic interventions.

Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice

ABSTRACTZika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations remain unknown. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate high Gas6 levels in the serum of patients with neurological complications which correlated with downregulation of genes associated with the type I IFN responses as consequence of Socs1 upregulation. Gas6 gamma-carboxylation is essential for ZIKV replication in monocytes, the main source of this protein. Gas6 also facilitates ZIKV replication in adult immunocompetent mice enabled susceptibility to transplacental infection and congenital malformations. Our data thus indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.

Neosporosis and toxoplasmosis are two prevalent and important protozoses in dairy cows in small farms from Thessaly, Central Greece

Neosporosis and toxoplasmosis are two significant protozoan parasitoses that can cause infertility and abortions in dairy cows worldwide. Those parasites, in contrary of other coccidia, are adapted to infect hosts by several routes of transmission. These include the consumption of sporulated cysts that have contaminated the environment, transplacental infection and accidental consumption of row meat infected with bradyzoites. Infertility, abortions, neonatal mortality and other clinical symptoms in cattle in both parasitoses can cause severe financial losses, especially when these diseases acquire an endemic or epidemic manner. The aim of this study was to report the prevalence of neosporosis and toxoplasmosis in dairy cattle as detected by ELISA technique, under the correlation with the age of infected animals. Blood samples were collected by venipuncture of the tail vein of 627 Holstein–Friesian dairy cows raised in 7 small farms (ranging from 55 the smaller to 137 the larger farm) from the region of Thessaly, central Greece. All farms have recorded a variety of infertility problems in the past. Animals were separated in three age groups; under 3 years old, between 3 and 6 years and over 6 years old. In a total of 627 cows from which the samples were taken and examined, 131 (20.89 %) of them were found positive for N. caninum while 51 (8.13 %) were positive for T. gondii. The prevalence in the three different age groups was recorded at 16.36%, 23.51% and 26.17% respectively for neosporosis and in the same age groups it was 5.20%, 9.16% and 13.08% respectively for toxoplasmosis. From the above results it becomes clear that preventative measures should be suggested to and adapted by the farmers, in order to decrease their financial losses.

Is perinatal CoVID-19 possible: first results

Among the problems associated with a new coronavirus infection, the possibility of its occurrence in pregnant women plays an important role. Until now, there is very little data on perinatal COVID-19, and there are no descriptions of structural changes in the afterbirth at all. Material and methods. A clinical and morphological analysis of 6 cases in which women with verified COVID-19 gave birth in an infectious hospital was performed. In all cases, the placenta was examined in detail morphologically using antibodies to the nucleoprotein and spike (S1 subunit spike protein) SARS-CoV-2. COVID-19 Results. It is shown that the clinical course of COVID-19 in pregnant women may be different, three were in the intensive care unit, including one was shown to be on a ventilator. 4 children were born at term, 2 children prematurely (at 31- 33 weeks of pregnancy). The condition of children in 5 nab. was assessed as satisfactory, only one child in serious condition was transferred to a children’s hospital. Intrauterine infection with the polymerase chain reaction documented in a single observation. When histological examination of the afterbirth in all observations, both in the maternal and fetal parts, changes characteristic of RNA viral infection was detected. Both of the studied antigens were found in moderate amounts in IHC. Conclusions. Intrauterine transplacental infection with a new coronavirus is certainly possible. Its frequency and clinical significance require further comprehensive study.

Chapter 7: TBE in special situations

TBE often takes a severe clinical course in immuno-suppressed patients. In transplant patients TBE usually takes a fatal course. TBE vaccination in immuno-suppressed patients can be non-effective TBE in pregnancy has rarely been reported; from recent cases there is no evidence of transplacental infection of the offspring. The alimentary route of infection of TBE is still common in some European countries resulting in a high clinical manifestation index. TBEV can be infectious in milk and milk products for up to 14 days under optimal environmental conditions. TBE is an important travel-related disease. Increasing numbers of non-endemic countries report imported cases. Imported TBE cases in non-endemic areas pose challenges regarding the diagnosis of TBE.