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Archive for the ‘Virology – Vector-borne DIsease’ Category

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Once herpes simplex infects a person, the virus goes into hiding inside nerve cells, hibernating there for life, periodically waking up from its sleep to reignite infection, causing cold sores or genital lesions to recur. Research from Harvard Medical School showed that the virus uses a host protein called CTCF, or cellular CCCTC-binding factor, to display this type of behavior. Researchers revealed with experiments on mice that CTCF helps herpes simplex regulate its own sleep-wake cycle, enabling the virus to establish latent infections in the body’s sensory neurons where it remains dormant until reactivated. Preventing that latency-regulating protein from binding to the virus’s DNA, weakened the virus’s ability to come out of hiding.

 

Herpes simplex virus’s ability to go in and out of hiding is a key survival strategy that ensures its propagation from one host to the next. Such symptom-free latency allows the virus to remain out of the reach of the immune system most of the time, while its periodic reactivation ensures that it can continue to spread from one person to the next. On one hand, so-called latency-associated transcript genes, or LAT genes, turn off the transcription of viral RNA, inducing the virus to go into hibernation, or latency. On the other hand, a protein made by a gene called ICP0 promotes the activity of genes that stimulate viral replication and causes active infection.

 

Based on these earlier findings, the new study revealed that this balancing act is enabled by the CTCF protein when it binds to the viral DNA. Present during latent or dormant infections, CTCF is lost during active, symptomatic infections. The researchers created an altered version of the virus that lacked two of the CTCF binding sites. The absence of the binding sites made no difference in early-stage or acute infections. Similar results were found in infected cultured human nerve cells (trigeminal ganglia) and infected mice model. The researchers concluded that the mutant virus was found to have significantly weakened reactivation capacity.

 

Taken together, the experiments showed that deleting the CTCF binding sites weakened the virus’s ability to wake up from its dormant state thereby establishing the evidence that the CTCF protein is a key regulator of sleep-wake cycle in herpes simplex infections.

 

References:

 

https://www.ncbi.nlm.nih.gov/pubmed/29437926

 

https://hms.harvard.edu/news/viral-hideout?utm_source=Silverpop

 

https://www.ncbi.nlm.nih.gov/pubmed/30110885

 

https://www.ncbi.nlm.nih.gov/pubmed/30014861

 

https://www.ncbi.nlm.nih.gov/pubmed/18264117

 

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Announcing our 10th e-Book on Amazon.com – 1st day, 9/4/2017

Editor-in-Chief: Aviva Lev-Ari, PhD, RN

 

On our Book Shelf on Amazon.com

WE ARE ON AMAZON.COM

https://www.amazon.com/s/ref=dp_byline_sr_ebooks_9?ie=UTF8&text=Aviva+Lev-Ari&search-alias=digital-text&field-author=Aviva+Lev-Ari&sort=relevancerank

http://www.amazon.com/dp/B00DINFFYC

http://www.amazon.com/dp/B018Q5MCN8

http://www.amazon.com/dp/B018PNHJ84

http://www.amazon.com/dp/B018DHBUO6

http://www.amazon.com/dp/B013RVYR2K

http://www.amazon.com/dp/B012BB0ZF0

http://www.amazon.com/dp/B019UM909A

http://www.amazon.com/dp/B019VH97LU

http://www.amazon.com/dp/B071VQ6YYK

https://www.amazon.com/dp/B075CXHY1B

 

The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications: VOLUME 2: Infectious Diseases and Therapeutics and VOLUME 3: The Immune System and Therapeutics (Series D: BioMedicine & Immunology) Kindle Edition – on Amazon.com since 9/4/2017

by Larry H. Bernstein (Author), Aviva Lev-Ari (Author), Stephen J. Williams (Author), Demet Sag (Author), Irina Robu (Author), Tilda Barliya (Author), David Orchard-Webb (Author), Alan F. Kaul (Author), Danut Dragoi (Author), Sudipta Saha (Editor)

https://www.amazon.com/dp/B075CXHY1B

 

Product details

  • File Size:21832 KB
  • Print Length:3747 pages
  • Publisher:Leaders in Pharmaceutical Business Intelligence (LPBI) Group; 1 edition (September 4, 2017)
  • Publication Date:September 4, 2017
  • Sold by:Amazon Digital Services LLC
  • Language:English
  • ASIN:B075CXHY1B
  • Text-to-Speech: Enabled 
  • X-Ray: Not Enabled 
  • Word Wise:Not Enabled
  • Lending:Enabled
  • Enhanced Typesetting:Not Enabled 

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Curator: Aviva Lev-Ari, PhD, RN

 

Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness

Published online: 26 July 2017

URMC Researchers Developing New Tool to Fight Antibiotic Resistance

Goal is to Distinguish Between Viral and Bacterial Infections, Reduce Unnecessary Use of Antibiotics

Friday, July 28, 2017

“It’s extremely difficult to interpret what’s causing a respiratory tract infection, especially in very ill patients who come to the hospital with a high fever, cough, shortness of breath and other concerning symptoms,” said Ann R. Falsey, M.D., lead study author, professor and interim chief of the Infectious Diseases Division at UR Medicine’s Strong Memorial Hospital.

“My goal is to develop a tool that physicians can use to rule out a bacterial infection with enough certainty that they are comfortable, and their patients are comfortable, foregoing an antibiotic.”

Lead researcher Ann Falsey, M.D.

Ann R. Falsey, M.D.

Falsey’s project caught the attention of the federal government; she’s one of 10 semifinalists in the Antimicrobial Resistance Diagnostic Challenge, a competition sponsored by NIH and the Biomedical Advanced Research and Development Authority to help combat the development and spread of drug resistant bacteria. Selected from among 74 submissions, Falsey received $50,000 to continue her research and develop a prototype diagnostic test, such as a blood test, using the genetic markers her team identified.

SOURCE

https://www.urmc.rochester.edu/news/story/5108/urmc-researchers-developing-new-tool-to-fight-antibiotic-resistance.aspx

Lower respiratory tract infection (LRTI)

We enrolled 94 subjects who were microbiologically classified; 53 as “non-bacterial” and 41 as “bacterial”. RNAseq and qPCR confirmed significant differences in mean expression for 10 genes previously identified as discriminatory for bacterial LRTI. A novel dimension reduction strategy selected three pathways (lymphocyte, α-linoleic acid metabolism, IGF regulation) including eleven genes as optimal markers for discriminating bacterial infection (naïve AUC = 0.94; nested CV-AUC = 0.86). Using these genes, we constructed a classifier for bacterial LRTI with 90% (79% CV) sensitivity and 83% (76% CV) specificity. This novel, pathway-based gene set displays promise as a method to distinguish bacterial from nonbacterial LRTI.

https://www.nature.com/articles/s41598-017-06738-3#Sec8

IMAGE SOURCE

https://www.nature.com/articles/s41598-017-06738-3#Sec8

 

SOURCES

http://sciencemission.com/site/index.php?page=news&type=view&id=microbiology-virology%2Fnew-tool-to-distinguish&filter=8%2C9%2C10%2C11%2C12%2C13%2C14%2C16%2C17%2C18%2C19%2C20%2C27&redirected=1&redirected=1

https://www.urmc.rochester.edu/news/story/5108/urmc-researchers-developing-new-tool-to-fight-antibiotic-resistance.aspx

https://www.nature.com/articles/s41598-017-06738-3

Bacterial or Viral Infection? A New Study May Help Physicians …

 

Other related articles published in this Open Access Online Scientific Journal include the following:

Series D, VOLUME 2:

Infectious Diseases and Therapeutics

Author, Curator and Editor: Larry H Bernstein, MD, FCAP and CuratorSudipta Saha, PhD

 

Series D, VOLUME 3:

The Immune System and Therapeutics

Author, Curator and Editor: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/biomed-e-books/series-d-e-books-on-biomedicine/human-immune-system-in-health-and-in-disease/

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Global Health Impacts of Vector-Borne Diseases: Workshop Summary | The National Academies Press

Reporter: Aviva Lev-Ari, PhD, RN

https://www.nap.edu/catalog/21792/global-health-impacts-of-vector-borne-diseases-workshop-summary?utm_source=NAP+Newsletter&utm_campaign=33f32c57d9-NAP_mail_new_2016_09_27&utm_medium=email&utm_term=0_96101de015-33f32c57d9-102340421&goal=0_96101de015-33f32c57d9-102340421&mc_cid=33f32c57d9&mc_eid=92753afd43

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Antibody shows promise as treatment for HIV

Aviva Lev-Ari, PhD, RN

 

 

 

 

Treating HIV with an antibody can reduce the levels of the virus in people’s bodies — at least temporarily, scientists report on 8 April in Nature1. The approach, called passive immunization, involves infusing antibodies into a person’s blood. Several trials are under way in humans, and researchers hope that the approach could help to prevent, treat or even cure HIV. The work is a milestone towards those goals, says Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. “This is an early study, but it’s a study with some impressive results,” he says.

 

Researchers tested four different doses of an HIV antibody called 3BNC117 in 29 people in the United States and Germany. Seventeen of the participants had HIV, and 15 of those were not taking antiretroviral (ARV) drugs at the time of the study. One infusion of the highest dose of antibody, given to 8 participants, cut the amount of virus in their blood by between 8 and 250 times for 28 days.

 

But much work remains to determine whether the approach can produce longer-lasting effects and whether it is practical for clinical use. Previous studies have shown that passive immunization can reduce levels of HIV in the blood of monkeys and mice, although the approach has not worked as well in humans2.

 

But the antibodies used in those earlier clinical tests were of an older generation that could not neutralize many different strains of HIV. Researchers have spent much of the past decade trying to find ‘broadly neutralizing’ antibodies that are more widely effective against the virus, and the 3BNC117 antibody belongs to this class.

 

The price of treatment with this approach is also a concern. Antibodies can cost thousands of dollars for each course of treatment, and the majority of people with HIV are in low- and middle-income countries, some of which are already fighting drug companies over the high cost of antibody medicines. “The practicality, utility and efficacy of this approach are hugely open questions,” says Mitchell Warren, executive director of AVAC, a global organization that advocates HIV prevention and is headquartered in New York City.

Source: www.nature.com

See on Scoop.itCardiovascular and vascular imaging

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Imaging the 3D structure of a single virus using the world’s most powerful x-ray free-electron laser

Reporter: Aviva Lev-Ari, PhD, RN

 

 

By measuring a series of diffraction pattern from a virus injected into an XFEL beam, researchers at Stanford’s Linac Coherent Light Source (LCLS) have determined the first three-dimensional structure of a virus, using a mimivirus.

 

X-ray crystallography has solved the vast majority of the structures of proteins and other biomolecules. The success of the method relies on growing large crystals of the molecules, which isn’t possible for all molecules.

 

“Free-electron lasers provide femtosecond X-ray pulses with a peak brilliance ten billion times higher than any previously available X-ray source,” the researchers note in a paper inPhysical Review Letters. “Such a large jump in one physical quantity is very rare, and can have far reaching implications for several areas of science. It has been suggested that such pulses could outrun key damage processes and allow structure determination without the need for crystallization.”

 

The current resolution of the technique (about 100 nanometers) would be sufficient to image important pathogenic viruses like HIV, influenza and herpes, and further improvements may soon allow researchers to tackle the study of single proteins, the scientists say.

 

Mimivirus is one of the largest known viruses. The viral capsid is about 450 nanometers in diameter and is covered by a layer of thin fibres. A 3D structure of the viral capsid exists, but the 3D structure of the inside was previously unknown.

Source: www.kurzweilai.net

See on Scoop.itCardiovascular Disease: PHARMACO-THERAPY

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Should Smallpox’s Last Two Samples Be Destroyed Or Preserved To Best Safeguard Humanity?

Reporter: Aviva Lev-Ari, PhD, RN

 

See on Scoop.itCardiovascular Disease: PHARMACO-THERAPY

Although the world hasn’t seen a case of smallpox in over 30 years, it isn’t quite gone yet. Two vials of the deadly virus remain: one in the United States and the other over 5,000 miles away in Russia. Experts around the world agree that these vials need to be destroyed at some point, but some believe that, for now, humanity is safer with the vials intact. Others insist their destruction is well overdue. The fate of the vials will be decided at an upcoming World Health Assembly meeting later this month.

 

Smallpox was arguably one of the most deadly diseases to ever exist. It is estimated to have killed up to 500 million people in the 20th century. Throughout time, it has probably killed more people than all other infectious diseases combined. By 1980, smallpox was eradicated, and today it remains the only disease to have been eliminated by the World Health Organization (WHO).

 

An opinion piece on the fate of the last two remaining strains of smallpox was released on PLoS Pathogens Thursday. In it, experts explain how research with the live smallpox virus is “not yet finished.” If the virus were to reappear, some researchers believe humanity is not prepared to fight it off. Although there is a vaccine against smallpox, it is in limited supply. This vaccine is also known to have a high rate of adverse and sometimes severe side effects. It can infect the brain and cause permanent damage. The International Business Times reports that the WHO’s original goals for a newer and safer vaccine, fully licensed antiviral drugs, and better diagnostics are still underway. The researchers believe that further screening and using new approaches such as genomics or proteomics can help enhance man’s preparedness against a possible smallpox resurgence.

 

So far, there have been two new antivirals that seem promising in treating smallpox. Neither has been licensed for use yet, and researchers feel they need live samples of the virus to continue their research. “Variola is unusual in that it is known to be a sole human pathogen, the viral and host factors responsible for this human-specific tropism remain essentially unknown to this day,” the researcher explained, IBT reported. Live samples of smallpox are also used to help understand other viruses and develop treatments for them.

 

Advances in synthetic biology mean that one day it may be possible to create smallpox from scratch. “The synthetic biology adds a new wrinkle to it. We now aren’t as sure that our countermeasures are going to be as effective as we’d though even five years ago,” Jimmy Kolker, Health and Human Services assistant secretary for global affairs told The Associated Press. Even if all traces of smallpox are essentially eliminated, there is still no saying that the virus won’t reappear again in the future. The researchers believe further observation of the living virus can help “to better respond to any future emergency situation resulting from a smallpox appearance.”

See on www.medicaldaily.com

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