Woke Retroviruses May Trigger Multiple Sclerosis and ALS

MedicalResearch.com Interview with:

Prof. Dr. Patrick Küry Dept. of Neurology Heinrich-Heine-University Düsseldorf Germany

Prof. Küry

Prof. Dr. Patrick Küry
Dept. of Neurology Heinrich-Heine-University
Düsseldorf Germany

MedicalResearch.com: What is the background for this study? How do these viruses in our DNA differ from others such as the herpes family of viruses?

Response: The background of our current two published studies is elucidating the role of endogenous retroviruses such as the HERV-W in contributing to neurological disease initiation and progression. Our new paper in PNAS (Kremer et al., PNAS 2019) describes a novel axon damage scenario for Multiple Sclerosis (MS) in which a “toxic” protein called ENV from HERV-W instructs so called microglial cells in the human brain to attack and damage myelinated axons.

Our second review article (Gruchot et al., Front Genet 2019) summarizes currently known effects on endogenous retroviruses exerted towards neural cells, that means cells other than the infiltrating immune cells. There is currently a shift of attention and research in the MS field in that resident neural cells such as oligodendrocytes, precursor cells, stem cells and microglial cells and their reactions are intensively investigated.

HERVs are evolutionary acquired retroviruses (RNA viruses able to integrate into host DNA via reverse transcription from RNA to DNA) that were collected during evolution by our ancestors. Some of them remained in our genome (8% of our genome is HERV related) and in most cases appear to be non-functional, mutated or genetically silenced. A few of them, as for example HERV-W in MS or HERV-K in ALS, can apparently be activated, woken up so to say, and one of the mechanisms leading to activation might be an infection by Herpesviruses. Note that herpesviruses such as for example the Epstein Bar Virus (EBV) are long known suspected triggers of MS, however, a direct correlation could never be demonstrated. HERVs such as HERV-W might therefore constitute the missing link.

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Bat Borne Nipah Virus Transmitted by Human Secretions

MedicalResearch.com Interview with:

Birgit Nikolay PhDMATHEMATICAL MODELLING OF INFECTIOUS DISEASESInstitut Pasteur

Dr. Nikolay

Birgit Nikolay PhD
MATHEMATICAL MODELLING OF INFECTIOUS DISEASES
Institut Pasteur 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Nipah virus was identified by the World Health Organization as an emerging infectious disease that may cause major epidemics if the pathogen evolves to become more transmissible, leading the organization to prioritize it for research to prevent future health emergencies. In the absence of efficient treatments or vaccines, the only way to control Nipah virus outbreaks is through targeted interventions that limit opportunities of spread. Designing such interventions is challenging in a context where transmission mechanisms remain poorly understood. The study provides important insights to better understand these mechanisms.

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Bats Carry Dangerous Viruses: Why Don’t They Get Sick?

MedicalResearch.com Interview with:
bats-mattaeMatae Ahn,MD-PhD candidate
Emerging Infectious Diseases (EID) Programme
Duke-NUS Medical School

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Bats, as the only flying mammals, are ‘special’ in their ability to host many highprofile viruses without suffering from disease. Such viruses including Ebola virus, Nipah virus and SARS or MERS coronaviruses, are highly pathogenic and often lethal to humans or animals, but yet cause no or minimal disease in bats. In addition, they also live very long relative to their small body size, despite elevated metabolic rates. However, what makes them special is still unclear.

In this study, we discovered dampened NLRP3-mediated inflammation in bats in response to both ‘sterile’ stressors and infection with three different types of zoonotic RNA viruses. We identified multiple molecular mechanisms of altered bat NLRP3, a critical regulator of virus-induced and age-related inflammation, as the cause. Importantly, the reduced inflammation had no effect on the viral loads, which suggests enhanced immune tolerance to infection in bats. Bats’ natural ability to dampen stress-related and virusinduced inflammation may be a key mechanism underlying their long lifespans and unique viral reservoir status.  Continue reading

Mono Virus Linked To Some Cases of Lupus

MedicalResearch.com Interview with:

John B. Harley, MD, PhD Professor and Director David Glass Endowed Chair Center for Autoimmune Genomics and Etiology (CAGE) Department of Pediatrics University of Cincinnati Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio 45229

Dr. Harley

John B. Harley, MD, PhD
Professor and Director
David Glass Endowed Chair
Center for Autoimmune Genomics and Etiology (CAGE)
Department of Pediatrics
University of Cincinnati
Cincinnati Children’s Hospital Medical Center
Cincinnati, Ohio 45229

MedicalResearch.com: What is the background for this study?

Response: Previous work has shown that Epstein-Barr virus infection is associated with systemic lupus erythematosus and studies of the origins of the autoimmune response have also suggested that the autoimmunity of this disease may originate with the immune response against this virus. In the meantime, many investigators have been studying the genetics of lupus over the past 25 years. They have found about 100 convincing genes that alter the risk of developing lupus.

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How Do Viruses Trigger Cough In Asthmatic Children, Even Without Allergies

MedicalResearch.com Interview with:

Giovanni Piedimonte, MD Steven and Nancy Calabrese Endowed Chair for Excellence in Pediatric Care, Research, and Education Professor & Chair of Pediatrics Cleveland Clinic Lerner College of Medicine Case Western Reserve University

Dr. Piedimonte

Giovanni Piedimonte, MD
Steven and Nancy Calabrese Endowed Chair for Excellence in Pediatric Care, Research, and Education
Professor & Chair of Pediatrics
Cleveland Clinic Lerner College of Medicine
Case Western Reserve University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study proves that asthmatic children already have a hyperactive calcium channel that’s extremely sensitive to environmental triggers.

If these children contract a virus, such as RSV, the hyperactive channel causes more severe symptoms that may require care in a hospital setting.

When a child developed asthma or bronchitis in the past, doctors thought these conditions could only be triggered by environmental allergens. There was no explanation why two out of three children ages five and under who wheeze and cough – and still test negative for allergies.

We needed to explore the mechanisms of the calcium molecule and the epithelial cells, which seem to trigger these symptoms without an allergic reaction. If the molecule’s behavior is producing the cough, we just need to figure out how to control the molecule to properly deactivate the cough mechanism in the asthmatic child

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Some Zinc Lozenges May Shorten Duration of Common Cold

MedicalResearch.com Interview with:

Dr-Harri-Hemilae.jpg

Dr. Harri Hemilä

Hemilä

Harri Hemilä, MD, PhD
Department of Public Health,
University of Helsinki

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Our meta-analysis of 3 randomized controlled trials on zinc acetate lozenges was motivated by an early trial which indicated that zinc lozenges might be more effective for patients with allergies.

We found that allergy, sex, age, and ethnic bacground did not influence the effect of zinc acetate lozenges.

Thus, the average effect of 3 day reduction in colds seems to be applicable for a wide range of common cold patients.

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Inflammation Caused By Mosquito Bites Helps Viral Infections Spread

MedicalResearch.com Interview with:
Clive McKimmie PhD
Research Fellow,
Virus Host Interaction Team (VHIT),
University of Leeds
St James’ University Hospital
Leeds UK

MedicalResearch.com: What is the background for this study?

Response: With the rapid spread of Zika in the Americas, attention has been drawn to this group of neglected mosquito-borne viral infections. The Zika virus is not alone in causing problems, others such as dengue and chikungunya viruses are infecting millions of people each year. Yet there’s little doctors can do to help people who get sick.
When mosquitoes bite you they can transmit these disease causing viruses. We don’t understand what happens during the early stages of infection very well. However, it is known that the mosquito bite itself somehow helps the virus to infect your body.

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Polyomaviruses May Raise Risk of Skin Cancer In Patients of Risk of Squamous Cell Carcinoma

MedicalResearch.com Interview with:
Anala Gossai BSc, MPH PhD candidate
Department of Epidemiology
Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
and co-authors

MedicalResearch.com: What is the background for this study? What are the main findings?

Gossai et al: Polyomaviruses (PyV) are potentially tumorigenic viruses in humans. However, limited data exists on the population seroprevalence or longitudinal serostability of PyVs, and individual characteristics that relate to seropositivity. Further, PyVs may be associated with the occurrence of cutaneous squamous cell carcinoma (SCC) – one of the most common malignancies in humans with increasing incidence reported in the US.

In a US nested case-control study, BK and JC seroreactivity was measured on 113 SCC cases and 229 matched controls who had a prior keratinocyte cancer. Repeated serum samples from controls, and both pre- and post-diagnosis samples from a subset ofsquamous cell carcinoma cases, were also assayed. Antibody response against each PyV type was measured using multiplex serology of recombinantly expressed VP1 capsid proteins. Among controls, BK and JC seroreactivity was stable over time, and there was little evidence of seroconversion following SCC diagnosis among cases. Odds of squamous cell carcinoma  associated with seropositivity to each PyV type were estimated using conditional logistic regression. JC seropositivity prior to diagnosis was associated with an elevated risk of SCC (OR=2.5, 95% CI: 1.2-5.2). 
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Norovirus and Enteroviruses May Be Resistant to Alcohol Based Hand Disinfectants

dr-erwin-duizer.pngMedicalResearch.com Interview with:
Erwin Duizer, PhD
Head of section Enteric Viruses
Centre for Infectious Diseases Control
National Institute for Public Health and the Environment
The Netherlands

Medical Research: What is the background for this study?

Dr. Duizer: Hand hygiene is important for interrupting the transmission chain of viruses through hands. Alcohol-based hand disinfectants are widely used in hospitals and healthcare facilities, due to convenience, rapidity, and broad acceptance by healthcare personnel. The effectiveness of alcohol-based hand disinfectant has been shown for bacteria and enveloped viruses but their effectiveness in reducing transmission of non-enveloped viruses, such as norovirus, is less certain. Therefore we tested, in a joint project of the RIVM and Wageningen University, the virucidal activity of a propanol based product and an ethanol based product in quantitative carrier tests. Additionally, the virus reducing effect of hand washing (according to health care guidelines) and the use the propanol based product was tested in a quantitative finger pad test. Continue reading

Protein Delivered By Gene Vector May Protect Against HIV-Like Viruses

Dr. Michael Farzan PhD Vice Chairman Department of Immunology and Microbial Science Florida Campus The Scripps Research InstituteMedicalResearch.com Interview with:
Dr. Michael Farzan PhD
Vice Chairman
Department of Immunology and Microbial Science
Florida Campus
The Scripps Research Institute

Medical Research: What is the background for this study?

Dr. Farzan: The key points are that HIV-1 needs two receptors – CD4 and CCR5 – to infect cells.  CD4’s primary job is to initially bind the viral entry protein, which upon CD4 binding, uncloaks its CCR5 binding site.   A number of years ago we observed that CCR5 had an unusual modification that was really important to HIV-1.  We later showed that antibodies – protein your body makes to protect from pathogens – mimics CCR5 by incorporating this modification.  We develop a peptide from one of these antibodies that mimics CCR5.

Medical Research: What are the main findings?

Dr. Farzan: By combined a soluble form of CD4 with this CCR5-mimicking peptide, we created a protein that neutralizes all HIV-1 isolates tested, including the hardest-to-stop viruses, as well as distantly related viruses found in monkeys.  It does so better than the best HIV-1 antibodies.  We expressed this protein using a commonly used gene-therapy vector, and showed that after a one-time inoculation we could protect from doses much higher than most humans are likely to see, and we did so 34 weeks after the inoculation.
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Diverse Herpes Viruses Share Ability To Suppress Immune Response

Christopher S. Sullivan, Ph.D. Associate Professor Dept. Molecular Biosciences The University of Texas at Austin anMedicalResearch.com Interview with:
Christopher S. Sullivan, Ph.D.
Associate Professor
Dept. Molecular Biosciences
The University of Texas at Austin and
Jennifer Cox, lead author Graduate student in Dr. Sullivan’s laboratory.
Jennifer Cox
, lead author
Graduate student in Dr. Sullivan’s laboratory.

Jennifer Cox’s Replies:

MedicalResearch: What is the background for this study? What are the main findings?

Jennifer Cox: In the last decade, researchers have identified that many viruses encode small regulatory molecules known as microRNAs. Some viral microRNAs are able to manipulate host processes including stress responses, proliferation, and cell death. However, there are many viral microRNAs with unknown functions. Many of the viruses that encode microRNAs are associated with severe pathologies including various cancers so understanding the role of viral microRNAs can shed light on virus biology.

For this study, we focused on identifying viral microRNAs that can regulate innate immune signaling for several reasons. First, all viruses have proteins to combat interferon signaling. Second, we have identified microRNAs from two diverse viruses (retro and annello) that can inhibit interferon signaling so we hypothesized that additional viral microRNAs will perform this same function. We screened ~70 viral microRNAs for the ability to regulate innate immune signaling and identified three herpesviruses, Epstein-Barr Virus, Kaposi’s Sarcoma Associated Virus, and Human Cytomegalovirus, that inhibit the interferon response.

Epstein-Barr Virus, causes an estimated 200,000 cancers every year, including lymphomas, nasopharyngeal cancers and some stomach cancers. Interestingly, most of these cancers harbor latent EBV – a state of limited gene expression that produces no virus. microRNAs are one of the few viral gene product expressed during latency.

Our further work identified that Epstein-Barr Virus, KSHV, and Human Cytomegalovirus have converged to inhibit interferon signaling in the same manner – through decreasing expression of a central hub of innate immune signaling, CREB binding protein (CBP). We show that this regulation conveys partial resistance to the negative effects of interferon treatment on an EBV+ lymphoma cell line. Additionally, removing the microRNA from a similar cell line increases the sensitivity to interferon.

Interferon can be used in combination with other chemotherapies to treat lymphomas but varies in success. Our results may partially explain the variability seen in patients with EBV-associated cancers.

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