Tetraspanins: Host Factors in Viral Infections.

Tetraspanins are transmembrane glycoproteins that have been shown increasing interest as host factors in infectious diseases. In particular, they were implicated in the pathogenesis of both non-enveloped (human papillomavirus (HPV)) and enveloped (human immunodeficiency virus (HIV), Zika, influenza A virus, (IAV), and coronavirus) viruses through multiple stages of infection, from the initial cell membrane attachment to the syncytium formation and viral particle release. However, the mechanisms by which different tetraspanins mediate their effects vary. This review aimed to compare and contrast the role of tetraspanins in the life cycles of HPV, HIV, Zika, IAV, and coronavirus viruses, which cause the most significant health and economic burdens to society. In doing so, a better understanding of the relative contribution of tetraspanins in virus infection will allow for a more targeted approach in the treatment of these diseases.

Viral and Prion Infections Associated with Central Nervous System Syndromes in Brazil.

Virus-induced infections of the central nervous system (CNS) are among the most serious problems in public health and can be associated with high rates of morbidity and mortality, mainly in low- and middle-income countries, where these manifestations have been neglected. Typically, herpes simplex virus 1 and 2, varicella-zoster, and enterovirus are responsible for a high number of cases in immunocompetent hosts, whereas other herpesviruses (for example, cytomegalovirus) are the most common in immunocompromised individuals. Arboviruses have also been associated with outbreaks with a high burden of neurological disorders, such as the Zika virus epidemic in Brazil. There is a current lack of understanding in Brazil about the most common viruses involved in CNS infections. In this review, we briefly summarize the most recent studies and findings associated with the CNS, in addition to epidemiological data that provide extensive information on the circulation and diversity of the most common neuro-invasive viruses in Brazil. We also highlight important aspects of the prion-associated diseases. This review provides readers with better knowledge of virus-associated CNS infections. A deeper understanding of these infections will support the improvement of the current surveillance strategies to allow the timely monitoring of the emergence/re-emergence of neurotropic viruses.

SARS-CoV-2, Zika viruses and mycoplasma: Structure, pathogenesis and some treatment options in these emerging viral and bacterial infectious diseases.

The molecular evolution of life on earth along with changing environmental, conditions has rendered mankind susceptible to endemic and pandemic emerging infectious diseases. The effects of certain systemic viral and bacterial infections on morbidity and mortality are considered as examples of recent emerging infections. Here we will focus on three examples of infections that are important in pregnancy and early childhood: SARS-CoV-2 virus, Zika virus, and Mycoplasma species. The basic structural characteristics of these infectious agents will be examined, along with their general pathogenic mechanisms. Coronavirus infections, such as caused by the SARS-CoV-2 virus, likely evolved from zoonotic bat viruses to infect humans and cause a pandemic that has been the biggest challenge for humanity since the Spanish Flu pandemic of the early 20th century. In contrast, Zika Virus infections represent an expanding infectious threat in the context of global climate change. The relationship of these infections to pregnancy, the vertical transmission and neurological sequels make these viruses highly relevant to the topics of this special issue. Finally, mycoplasmal infections have been present before mankind evolved, but they were rarely identified as human pathogens until recently, and they are now recognized as important coinfections that are able to modify the course and prognosis of various infectious diseases and other chronic illnesses. The infectious processes caused by these intracellular microorganisms are examined as well as some general aspects of their pathogeneses, clinical presentations, and diagnoses. We will finally consider examples of treatments that have been used to reduce morbidity and mortality of these infections and discuss briefly the current status of vaccines, in particular, against the SARS-CoV-2 virus. It is important to understand some of the basic features of these emerging infectious diseases and the pathogens involved in order to better appreciate the contributions of this special issue on how infectious diseases can affect human pregnancy, fetuses and neonates.

Significance of the placental barrier in antenatal viral infections.

The placenta provides a significant physical and physiological barrier to prevent fetal infection during pregnancy. Nevertheless, it is at times breached by pathogens and leads to vertical transmission of infection from mother to fetus. This review will focus specifically on the Zika flavivirus, the HIV retrovirus and the emerging SARS-CoV2 coronavirus, which have affected pregnant women and their offspring in recent epidemics. In particular, we will address how viral infections affect the immune response at the maternal-fetal interface and how the placental barrier is physically breached and discuss the consequences of infection on various aspects of placental function to support fetal growth and development. Improved understanding of how the placenta responds to viral infections will lay the foundation for developing therapeutics to these and emergent viruses, to minimise the harms of infection to the offspring.

Global health security as it pertains to Zika, Ebola, and COVID-19.

PURPOSE OF REVIEW: Due to the impact of the COVID-19 pandemic this past year, we have witnessed a significant acceleration in the science, technology, and policy of global health security. This review highlights important progress made toward the mitigation of Zika, Ebola, and COVID-19 outbreaks. These epidemics and their shared features suggest a unified policy and technology agenda that could broadly improve global health security. RECENT FINDINGS: Molecular epidemiology is not yet in widespread use, but shows promise toward informing on-the-ground decision-making during outbreaks. Point-of-care (POC) diagnostics have been achieved for each of these threats; however, deployment of Zika and Ebola diagnostics lags behind those for COVID-19. POC metagenomics offers the possibility of identifying novel viruses. Vaccines have been successfully approved for Ebola and COVID-19, due in large part to public-private partnerships and advance purchase commitments. Therapeutics trials conducted during ongoing epidemics have identified effective antibody therapeutics for Ebola, as well as steroids (both inhaled and oral) and a broad-spectrum antiviral for COVID-19. SUMMARY: Achieving global health security remains a challenge, though headway has been made over the past years. Promising policy and technology strategies that would increase resilience across emerging viral pathogens should be pursued.

Pregnancy and pandemics: Interaction of viral surface proteins and placenta cells.

Throughout history, pandemics of infectious diseases caused by emerging viruses have spread worldwide. Evidence from previous outbreaks demonstrated that pregnant women are at high risk of contracting the diseases and suffering from adverse outcomes. However, while some viruses can cause major health complications for the mother and her fetus, others do not appear to affect pregnancy. Viral surface proteins bind to specific receptors on the cellular membrane of host cells and begin therewith the infection process. During pregnancy, the molecular features of these proteins may determine specific target cells in the placenta, which may explain the different outcomes. In this review, we display information on Variola, Influenza, Zika and Corona viruses focused on their surface proteins, effects on pregnancy, and possible target placental cells. This will contribute to understanding viral entry during pregnancy, as well as to develop strategies to decrease the incidence of obstetrical problems in current and future infections.

Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis.

Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins' functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.

The Zika virus: Lurking behind the COVID-19 pandemic?

WHAT IS KNOWN AND OBJECTIVE: The sudden and extensive outbreak of coronavirus (SARS-CoV-2) has overshadowed another developing viral threat: the Zika flavivirus. Of particular concern is that pregnant women can pass Zika virus to the foetus, and there is a strong implication of an association between Zika virus infection and foetal microcephaly. Currently, there is no vaccine, and there is no cure. METHODS: Published literature and Internet sources were searched for information related to Zika virus, its transmission, its clinical presentation and sequalae, prevention and implications (practice and regulatory) for healthcare providers. The identified English sources were reviewed, assessed and synthesized. Emphasis was placed on providing an overview of the problem, and identification of unmet needs and future directions. RESULTS AND DISCUSSION: Zika virus poses a major challenge for healthcare providers, particularly in areas unaccustomed to it, since it is transmitted to humans by the vector Aedes aegypti mosquito. The outbreak impacts every healthcare provider, because every provider is required to report cases of Zika infection to their state or local health agencies--whether the infection is confirmed or merely suspected. Since the virus has become a worldwide crisis, healthcare providers will need to work across national boundaries and medical disciplines in order to educate patients about Zika symptoms and the mosquito vector. Until further information is known, infected patients (male and female) are being advised to avoid conceiving a child. WHAT IS NEW AND CONCLUSION: Until a vaccine is developed or effective treatment for Zika virus is discovered, healthcare providers must be AVP (aware, vigilant and proactive) in order to lessen the spread and impact of the implicated devastating birth defects (microcephaly) and other neurological disorders (eg Guillain-Barré Syndrome) of this infection. Unfortunately, many knowledge gaps exist. There is an urgent need for a reliable, inexpensive diagnostic test, an effective treatment and an approved and readily available vaccine.

Extracellular Vesicles in the Pathogenesis of Viral Infections in Humans.

Most cells can release extracellular vesicles (EVs), membrane vesicles containing various proteins, nucleic acids, enzymes, and signaling molecules. The exchange of EVs between cells facilitates intercellular communication, amplification of cellular responses, immune response modulation, and perhaps alterations in viral pathogenicity. EVs serve a dual role in inhibiting or enhancing viral infection and pathogenesis. This review examines the current literature on EVs to explore the complex role of EVs in the enhancement, inhibition, and potential use as a nanotherapeutic against clinically relevant viruses, focusing on neurotropic viruses: Zika virus (ZIKV) and human immunodeficiency virus (HIV). Overall, this review's scope will elaborate on EV-based mechanisms, which impact viral pathogenicity, facilitate viral spread, and modulate antiviral immune responses.

Working Hard or Hardly Working? Regulatory Bottlenecks in Developing a COVID-19 Vaccine.

Vaccine solutions rarely reach the public until after an outbreak abates; an Ebola vaccine was approved 5 years after peak outbreak and SARS, MERS, and Zika vaccines are still in clinical development. Despite massive leaps forward in rapid science, other regulatory bottlenecks are hamstringing the global effort for pandemic vaccines.