Friday, February 21, 2020


Why is the Coronavirus Hitting Men Harder than Women?

Women are building stronger immune responses to infection, scientists say, and in far greater numbers smoke in people. The coronavirus that originated in China has spread anxiety and fear throughout the world. But while the novel virus largely spared one vulnerable group kids it seems to pose a particular threat to middle-aged and older adults, especially men.
The Chinese Center for Disease Control and Prevention conducted the largest study of cases involving coronavirus to date this week. Although men and women were infected in roughly equal numbers, researchers found that the mortality rate among men was 2.8 percent compared to 1.7 percent among women. Men were also disproportionately impacted during outbreaks of SARS and MERS caused by coronaviruses. In Hong Kong in 2003, more women than men were diagnosed with SARS but, according to a study published in the Annals of Internal Medicine, the mortality rate among men was 50 percent higher.




In the current outbreak, scientists say, there may be a number of factors working against men, including some biological ones, and some lifestyle rooted ones. Men are the weaker group when it comes to building an immune response to infections.
"This is a trend we've seen with other viral respiratory tract infections  men can have worse results," said Sabra Klein, a scientist at the Johns Hopkins Bloomberg School of Public Health who studies sex differences in viral infections and vaccine responses. This is what we have seen with other viruses. Women better fight them off, "she said. Women also produce stronger immune responses after vaccination and have increased immune responses to memory that protect adults from pathogens to which they were exposed to as children.
"There's something more exuberant about the immune system in females," said Dr Janine Clayton, director of the National Institutes of Health's Office of Research on Women's Health.

Thursday, February 13, 2020


How the virus affect younger, seemingly healthy individuals
Researchers are still working out how the virus acts at this point in time.
"There are early days when it comes to how the COVID-19 virus communicates with the body and how it causes symptoms and sometimes kills people," says Vikram Misra, professor at the University of Saskatchewan's department of microbiology in Saskatoon.
Here are a few things we do know. The novel virus is part of a family of viruses called coronaviruses. Named for their telltale crown-like spikes, they mainly infect bats, pigs, and small mammals, but can migrate from animals to humans and from one human to another.
Many pathogens can infect humans, including two that have proved extremely deadly: SARS (Severe Acute Respiratory Syndrome) and MERS, or Respiratory Syndrome in the Middle East.
When COVID-19 enters the body — through droplets in the air — it appears to be bound to a particular lung tissue receptor. From there, it “hijacks” the host cell’s mechanisms to make more copies of itself. Tissue damage happens as a result of viruses taking over the cell completely, causing it to die, or when immune cells mount a defense against the viral infection, leading to cell death.


If huge numbers of cells die, then the affected organ, in this case, the lung can’t function effectively.
“Typically, coronavirus causes respiratory infections,” says Matthew S. Miller, associate professor at Michael G. De Groote Institute for Study on Infectious Diseases at the McMaster Immunology Research Centre, McMaster University. Modern coronaviruses infecting humans every year typically cause moderate, uncomplicated upper respiratory infection.
“The different and unique about the virus that’s causing this outbreak is that it can cause acute respiratory distress,” says the head of the university’s Miller Laboratory. “That means that the patient’s lungs can accumulate fluid, for example, which is more typical of pneumonias. It’s the respiratory failure or cardio-respiratory issues that lead to patients dying.”
Those with serious COVID-19 cases undergo a clinical syndrome, known as a "cytokine storm," says Miller. The term describes an overproduction of immune cells (cytokines) and their activating compounds. A flood of activated immune cells comes into the lungs.
This essentially means too much of a good thing: The strength of the immune response can put a healthy person at risk for complications associated with respiratory illness.
“The immune system overacts with the infection, and it's the immune system that causes lung damage rather than the virus itself, "says Miller. “Cytokine a storm is also consistent with the disease that SARS caused and is also consistent with what we sometimes see in people who are severely ill with influenza virus infection.


“An immune system the analogy might be: Instead of using a fly swatter to squash a fly you use a sledgehammer and punch a hole in the wall,” he says.
The lungs are highly vascularized, Miller explains: There’s a lot of blood flow in the lungs, because they’re the site of gas exchange. Normally, you want your airways to be relatively dry so that you can breathe in air, which gets transferred to red blood cells and carried to the rest of the body.
“During infections or immune responses, the tissue becomes damaged, then the fluid that’s normally contained in the blood vessels starts to leak into airways,” Miller says. “That build-up of fluid in the lungs are what can cause breathing distress because now lungs aren’t exchanging gas very efficiently.”
Cytokine storms can have other effects on the lungs, such as inflammation.
“You can have a lot of inflammation in your lungs' says Misra. “Inflammation is always a bad thing. With 1918 the influenza virus that killed millions of people, experiments done in the last 10 years show that inflammation was the killer in that case as well, because of the cytokine storm.”

Wednesday, January 29, 2020

DID Novel DNA-Sensing Pathway Found in Human Cells, Absent in Mice


Researchers at The University of Washington have discovered a unique novel DNA-sensing the pathway that launches an antiviral response to foreign genetic material in human cells.
Triggered by an enzyme called DNA protein kinase (DNA-PK), and the newly invented pathway is independent of cGAS-STING pathway until now considered as the most regulator of mammalian innate immune responses to DNA and it is missing or inactive in mouse cells. The finding raises a question about the promise of therapies that focus on cGAS-STING for immune modulation, researchers report in Science Immunology.
“It seems like a DNA-sensing a pathway that been completely overlooked—probably because much of the research has been done used murine systems,” says Christian Holm, who researches cGAS-STING at Aarhus University and wasn’t involved within the study. Previous work on antiviral responses has focused exclusively on cGAS-STING, he adds. “Now this comes along and says there’s this other pathway . . . that seems to be completely independent of STING and may be very important.”
It makes perfect sense to have another DNA-sensing mechanism.—Alexiane Decout, EPFL    

First described in 2013, the cGAS-STING pathway plays a critical role within the cell’s innate response to viral infection. Upon detecting cytosolic DNA (usually a tell-tale sign of viral entry), the cGAS enzyme binds to the transmembrane protein STING to trigger the assembly of interferons and other antiviral responses.
The pathway has become a well-liked target in drug development, with researchers trying to harness STING’s activity for cancer immunotherapy or to calm it in autoimmune diseases within which innate immune responses are overactive.
The University of Washington’s Dan Stetson tells Scientist that he and his team were studying with the effects of tumor-promoting viruses on cGAS-STING once they stumbled across the novel pathway. Graduate Katelyn Burleigh generated human cell lines lacking STING, he says, and located that they are still produced interferons when transfected with foreign DNA. Further assays using various human cell types and chemical inhibitors indicated that DNA-PK, an enzyme known for its role in detecting and responding to DNA damages within the nucleus were sensing that foreign DNA within the cell cytoplasm and launching its own, STING-independent response.
It’s not the primary time DNA-PK has been implicated in antiviral defenses. The University of Cambridge’s Geoffrey Smith and Brian Ferguson declared in 2012 that DNA-PK in mouse and human cells will promote interferon production in response to transfection with foreign DNA. However, that study concluded that DNA-PK probably triggered the response through STING, not independently of it.
“It’s nice to check that another group has found a crucial role for DNA-PK in sensing foreign DNA,” Smith tells The Scientist, adding that the Washington team’s paper presents The data concerned "considers STING-independent new pathway.
He notes that assays the team carried out using DNA-PK inhibitors perceived to influence antiviral responses differently depending on cell type—a result that Stetson says might need to do with interactions between the DNA-PK and gCAS-STING pathways within the various cell lines the team used. In some cases, “the two pathways may antagonize each other,” Stetson writes an email to The Scientist. “It is something we are interested in pursuing.”
Examining other mammalian cell lines, Stetson’s team founded evidence of the novel DNA-PK pathway in non-human primate cells and in rat cells. However, researchers were unable to identify the pathway in mouse cells, where most preclinical research on cGAS-STING therapy the research was conducted.
Alexiane Decout, a research scientist studying STING at EPFL in Switzerland who saw a preprint of the paper on bioRxiv, last year says she’s unsurprised by the finding because previous studies have already shown variations between human and mouse antiviral responses. “The mouse cGAS-STING pathway is far more easily activated then the human one,” she says as a result of that pathway’s lower activation in human cells, “it makes perfect sense [that those cells] have another DNA-sensing mechanism.”
This seems to be a largely neglected DNA-sensing pathway, Christian Holm, University of Aarhus.
The presence of this second the mechanism could have implications for efforts to modulate innate immune responses in patients with an autoimmune disorder. Stetson and colleagues propose in their paper that drugs designed to dampen cGAS-STING activity might be got to be paired with DNA-PK inhibitors (many of these are in clinical development) to be effective although, given an additional role in DNA repair, it is not clear how feasible such inhibition would be.
There also are potential applications for the novel DNA-sensing pathway in immunotherapy, notes Leticia Corrales, who has patent applications on STING-targeting compounds for cancer treatment and works at the pharmaceutical company Boehringer Ingelheim in Vienna.
She says that improving the innate immune response through DNA-PK may help to promote antitumor immunity. However, “first we have to verify that in humans this pathway has relevancy for antitumor immune responses,” she says, adding that researchers would need to be “very cautious about the toxicity aspects of using this approach.”
Stetson, who incorporates a patent-pending on DNA-PK modulation for disease treatment, says that his team is now exploring whether the newly discovered pathway promotes immunity to viral infection, and how the DNA-PK enzyme manages its dual roles of promoting repair of DNA damage within the nucleus and triggering responses to foreign DNA within the cytoplasm. 
For therapeutic purposes, “The long-term goal should be worked out a way to manipulate that,” he says, “and deliberately turn into what normally would be repaired into an extremely potent innate immune response.”
Previously demonstrated that the viral oncogenes of the DNA tumor viruses are potent antagonists of the cGAS-STING DNA sensing pathway, here, as per the report unexpected finding that the E1A oncogene of human adenovirus 5 blocks two distinct intracellular DNA sensing pathways in human cells: the well-known cGAS-STING pathway and a second, STING-independent DNA sensing pathway (SIDSP). Human cells have a second intracellular DNA pathway of sensing with implications for host defense, autoimmunity, and antitumor immunity.

Friday, January 24, 2020

IMMUNE RESPONSE 2020

About Conference


Me Conference takes immense pleasure to welcome all the participants around the globe to our “2nd International Conference on Viral Infection and Immune Response” scheduled during June 25-26, 2020 in Abu Dhabi, UAE with that highlights on many research related to Viral Infection and Immune Response.
Immune Response 2020 brings together immunologists, Virologists, and Researchers to discuss about the challenges and various progress in the field of Immunology and Virology. The aim of the conference is to provide an international platform to Immunologists, Virologists, research scholars, Virology and Immunology professors and academics for discussion and implementation of the recent research in Immunology and Virology for attaining sustainable development in local and global contexts.
On behalf of Immune Response 2020, we invite you to join us for the academic discussion and visit the beautiful city of Abu Dhabi, UAE.