Novel siRNA gene therapy targets HIV evasion system - [XZ - W8]

 

Researchers learned the value of mRNA during COVID vaccines, now they are trying to apply this to HIV. 

Recently, associate professor Emmanuel Ho has developed a novel nanomedicine based on siRNA in gene therapy. Normally, HIV produces a protein called Nef which prevents autophagy, the process by which the body gets rid of pathogens. In addition, the gene CCR5 in HIV assists viral entry into cells. 

The new gene therapy, a ph-sensitive dual preventative siRNA-based nanomicrobicide targets both the Nef and CCR5 gene and prevents infection in vaginal CD4+ cells. The therapy is composed of siRNA-PEI encapsulated PLGA-PEG nanoparticles and knocks down both genes. The siRNAs are mainly released in neutral pH conditions.

Retrovirus found to be a key player in ancient myelination -- LL

 https://www.sciencenews.org/article/ancient-retrovirus-myelin-speedy-nerves-evolve 

Retrovirus found to be a key player in ancient myelination

Research shows that an ancient retrovirus helped activate the production of a protein encoding myelin. Myelin helps insulate nerve fibers, and is a coating of fat and protein which protects axons, which may have increased the complexity and speed of the brain. These coated nerves also allowed fibers to grow thinner and longer, which may have contributed to an augmentation in the size of animals. The retrovirus is embedded in the DNA of jawed vertebrates. Retroviruses are RNA viruses that embed themselves in the DNA of cells, meaning they can occasionally (albeit rarely) become part of the genetic material passed down from generation to generation. 

The researchers were able to make this connection since they found high levels of the retrovirus in cells that compose myelin. Though the RNA (dubbed RetroMyelin) from the retrovirus doesn’t directly code the information for making myelin, it latches on to a protein that starts myelin production. Furthermore, when quantities of RetroMyelin were reduced in jawed vertebrates, the production of myelin dropped.

-LL

New Study Says Herpes May Double Risk of Dementia - LL

 https://www.sciencealert.com/herpes-virus-may-double-your-risk-of-dementia-study-finds 

New Study Says Herpes May Double Risk of Dementia

A new study examined more than 1,000 70-year olds in Sweden, and determined that having Herpes Simplex Virus 1 (HSV-1), the same virus that causes cold sores, can double the risk of having dementia. Around 80% of adults in Sweden have been exposed to HSV-1 at some point. 

Currently, the main causes of Alzheimer’s disease (a type of dementia) are age and APOE-4, a genetic variant. The significance of this study is that it indicates that certain viruses could increase likelihood of future cognitive decline. This is in line with the theory that dementia could be an out-of-control immune response to certain antigens, which has been a lowly-regarded scientific theory since the early 1900s. However, there is research pointing in the direction of HSV-1: unusually high levels of the virus have been found in the brains of people who succumbed to Alzheimer’s. 

However, there isn’t enough substantive evidence to implicate HSV-1 in development of neurodegenerative diseases. Some research indicates the opposite, and some neuroscience research fails to include microbiology experts. 

-LL

Avian protein bundle up to enhance reproduction in human cells - [XZ - W7]

Avian flu use a reproductive aid protein called ANP32 protein, which causes the virus to jump from birds to mammals. These proteins are found to be tucked into viral particles and help recruit proteins to form polymerases in mammalian cells.

In mammalian cells, researchers have found that some bird ANP32 proteins are attached to the virus; researchers suspect that the viral particles is attached to the polymerase and gets bundled into the viral particle along with the rest of the machinery

However, a question remains regarding the mechanisms that the virus uses to invade mammalian cells. Two likely hypotheses for the mechanisms include: 1. Mutations caused the virus to be able to mobilize human/mammalian ANP32; 2. Avian ANP32 are tucked into viral particles that aid reproduction in mammals. 

Highly pathogenic H5N1 detected in Gentoo Penguin -- LL

Article:

 https://www.nytimes.com/2024/01/30/science/antarctica-bird-flu-penguins.html

For the first time, a dead Antarctic penguin tested positive for a version of bird flu called H5N1. The H5N1 bird flu is a highly pathogenic virus that originally cropped up in 2020, eventually spreading to the tip of South America, which is how it likely made its way to Antarctica — specifically, the Falkland Islands, a British-owned territory and breeding ground for gentoo penguins. Since the penguins have likely never been exposed to the virus before, they have little immunity. Further danger is attributed to the fact that they breed in crowded groups, increasing the transmission rate from penguin to penguin.

The penguins are already threatened by numerous forces, including “climate change, pollution, and commercial fishing”, as stated by the New York Times. The virus hasn’t been found in any other local penguin species yet — including Rockhopper, Emperor, and Macaroni penguins — but its spread could be catastrophic. When the virus reached South America, thousands of deaths of Humboldt penguins were reported from Chile. 

–LL

Bacteriophages in Gut May Help Regulate Stress

 Bacteriophages in Gut May Help Regulate Stress

https://www.theguardian.com/science/2024/feb/05/viruses-living-human-gut-help-regulate-stress-study 

A new Ireland study indicates that some of the bacteriophages living in guts help regulate and control stress-induced issues in our bodies. (As a side note, bacteriophages are a type of virus that infect bacteria). The study placed mice in socially stressful situations such as overcrowded living. Then, they took bacteriophages from normal, unstressed mice, and transplanted them into the stressed mice, which reduced the levels of their stress hormones. More research needs to be done to see whether this has the same effect on humans, but it’s interesting to consider the connection between gut viruses and anxiety/stress/depression.

-LL

Stomach Virus Spread in Texas -- LL

 https://www.cbs19.tv/video/news/local/501-49b7dee3-6937-4f49-9259-2deb9f35964a 

A stomach virus has been rapidly spreading across the state of Texas, leading some school districts to cancel classes. The virus, potentially adenovirus or norovirus, is likely spread through contact with infected people, contaminated food, or well used surfaces. According to doctors, symptoms (which may include fever, cramping, diarrhea, among others) are expected to improve after 5 days to a week. 

-LL

Most Widely Circulating COVID Variant : JN.1 -- LL

https://www.npr.org/2024/01/25/1226770948/covid-jn-1-most-prevalent-variant 

Currently, the most widely circulating variant of COVID-19 in the US is a mutation called JN.1, which is a subvariant of Omicron. According to the Centers for Disease Control and Prevention (CDC), it now makes up 86% of recorded COVID-19 cases. The symptoms are similar to that of other COVID-19 variants, including coughing, sore throat, fever, among others. The recommended precautions are also familiar: wear masks, avoid crowded areas, and if you’re sick, stay home. The current COVID booster can help protect against these mutant strains, but vaccination rates among adults remain remarkably low. Since so few people are vaccinated (an issue for another post!) the surge has been especially prominent.

-LL

Zika virus cross into human through nanotube formation - [XZ - W6]

Joyce Jose, assistant professor at Penn State, and her team are launching new research on nanotube tunneling process influencing transmission of Zika virus from the mother to the fetus.

In their previous research, they identified that prior to tunneling, Zika cells use a "lock and latch" method by two Zika proteins: a capsid and a viral membrane protein which connect to stabilize virus for infection.

Recently, these Jose and her team discovered that maternal cells infected with the Zika virus create connections called tunneling nanotubes, that extend to uninfected cells, both maternal and fetal. In addition to transmission, this mechanism is suspected to evade the immune system

The protein non-structural protein 1(NS1) interacts with human cells to form nanotubes; these researchers even identified components of the virus, pieces of RNA material and protein inside the nanotubes. 

Next, they plan to look at the action of these nanotubes in pregnant mice.

Humans survived in symbiosis with ancient viruses [XZ - W5]

Endogenous retroviruses are estimated to make up 8-10% of the human genome. Up until now, scientists thought the materials were unusable or harmful. However, a critical early stage of embryonic development has been linked to a virus that mixed with our ancestral DNA. The newly discovered link has significances for creating artificial embryos and regenerative medicines.

Scientists identified a retroviral MERVL-gag protein expression which influences the gene URI, thought to enable cells to become pluripotent. MERVL-gag is high in the early phase of totipotent growth, then steadily decreases as URI becomes more influential on the behavior of cells. 

The retroviral protein is found to help development of totipotent cells into pluripotent cells in mouse models. In other words, the protein enables specialization in the embryo and determines whether a blob of cells become a human, cat or sea cucumber. 

This finding is significant in uncovering the long symbiotic relationship between humans and viruses, especially through retroviral protein that co-evolved will us for millions of years.

Ebola can enter cells through tunneling [XZ - W4]

Scientists have found a new way with which Ebola virus enters cells; Using live scanning electron and high-resolution 3D-microscopy, Dr. Shtanko and her team showed that Ebola infected cells using a tunneling nanotubes containing viral particles to infect other cells.

Originally, scientists thought that Ebola uses the general model of infection, where after replication, the virus is released into the body to continue infecting other cells. However, tDr. Shtanko and her team suggested a new method: Ebola-infected cells enhance the formation of tunneling nanotubes, which transferred viral particles to other cells. 

Not only was the full virus not required to trigger tunneling (only small sections of proteins coding for individual proteins were needed), more importantly, this phenomena occurred in cells undergoing treatment with entry inhibitors or treatments for the virus. Currently, how the particles are transmitted still remains unknown, yet the team plans to continue looking for answers using laser micro-dissection, mass spectroscopy and and low-abundance RNA seq. 

Dr. Shtanko will also explore whether similar viruses such as Sudan and Marbug exploit similar entry mechanisms.

Measles Resurge could be a sign of decrease in vaccination in schools [XZ - W3]

Nearly a dozen measles cases have popped up in the United States in PA, VA and GA in the past weeks. The Philadelphia Department of Public Health has confirmed at least 9 cases over the past month.

Measles is currently the most infectious disease known. Measles spread through cough, sneeze, runny nose; the illness spreads as red lesions across the trunk of the body. Measles could also pose serious health risks to young children or children with compromised immunity. 

Measles was eliminated in the US in 2000. However, small outbursts still occur in the States because measles was not eliminated worldwide. Experts suspect that unvaccinated individuals in the States are contracting measles while traveling abroad.

In addition, vaccination rate in grade school children (92% vaccinated compared to federal limits 95%) remains low. CDC reported that the majority of the measles cases were among age eligible children and adolescents who had not been vaccinated. 

Typically, measles treatment involve hospitalization, however, severe measles could also be treated with vitamin A to support the immune system.

Ancient permafrost virus have been recovered [XZ - W2]

The ancient permafrost virus methuselah microbes, or zombie virus have recently been isolated from the Arctic by scientists and suspected to cause a major disease outbreak due to global warming. 

Scientists are calling for attention to viruses that originate in the North, as prior analysis of pandemic threats have focused on diseases spreading from South. Many scientists also believe that there's an increasing risk to permafrost virus outbreaks as global warming progresses. Although some viral strains isolated from Siberia has only been shown to affect single celled organisms like amoeba, much is unknown about the infectivity of other viruses. 

Indeed, geneticist Jean-Michel Claverie fo Aix-Marseille University cautioned that genomic traces of human pathogens, for example poxviruses and herpes viruses have been found. Yet the question remains whether the genetic remains of these viruses still retain pathogenicity. In addition, it may not be the melting permafrost that directly poses the most immediate risk. Disappearance of the Arctic sea ice could enable trade and deep drilling for oil and ores can also release a vast amount of pathogens.

Nevertheless, scientists have begun to plan for an Arctic monitoring network. 

Antibodies found which target HIV fusion protein [XZ - W1]

Three different antibodies have been found to protect monkeys from HIV in a placebo-controlled proof of concept study. A human antibody and two monkey antibodies were found to be able to target the fusion peptide on the virus which assists viral entry.

The vaccine research center (VRC) at the National Institute of allergy and infectious disease (NIAID) isolated a fusion peptide derived antibody VRC34.01 and two antibodies from rhesus macaques DFPH-a.15 and DF1W-a.01 who received vaccination designed to generate fusion peptide derived antibodies and validated the protective effects of the antibodies via the simian-HIV (SHIV) challenge. 

By infusing four groups of monkeys (three groups received single intravenous infusion of one type of antibody, one group receiving a placebo), researchers found that all monkeys with the placebo acquired SHIV, while other groups demonstrated varying levels of protection from SHIV. In addition, a higher dose of infusion 10mg/kg compared to 2.5 mg/kg was correlated with a stronger protective effect.

Injecting Contaminated Cadaver Hormones Could Lead to Alzheimer's (ES - W5)

Article: https://www.nbcnews.com/health/health-news/human-growth-hormone-shots-cadavers-linked-alzheimers-study-finds-rcna135927

It's possible that Alzheimer's may have more in common with CJD than previously thought - they both may be caused by contaminated medical procedures.

Particularly those from cadavers.

Before the US adopted a synthetic version 1985, treatment for short-stature individuals involved a hormone taken from the pituitary glands, located at the base of the brain. Extracting this hormone, however, sometimes led to the unintended extraction of amyloid-beta protein. Amyloid-beta protein is found in Alzheimer's brain plaques, and studies on animals show that an excess amount of these proteins trigger plaque creation.

The study's claims are based on limited data; it's based on only 5 dementia patients ages 38-55 (none with genetic mutations that indicated an early-onset), and over 7,700 children were given this early growth hormone from 1959 to 1985, 27,000 worldwide (Szabo). Thus, it is likely that there is a little risk for Alzheimer's, else there would be more cases.

Focus on Alzheimer's and contaminated medical procedures stems from concerns over Creutzfeldt-Jakob disease (CJD), which is very similar to Mad Cow Disease. People became infected after receiving hormone samples contaminated with prions - "little-understood proteins that can trigger normal brain proteins to fold into abnormal shapes," (Szabo). So far, the US has had 35 patients die from CJD after receiving a cadaver-derived growth hormone.

This is also why, until lifted by the FDA in 2022, people from the UK (which, historically, has had many cases of Mad Cow Disease) could not donate blood to patients in the US. 

It's important to note no links have been found between organ transplants and risk of Alzheimer's, or that donated blood increases amyloid protein/risk of Alzheimer's.

Phages - Hope Against Antibiotic-Resistant Bacteria? (ES - W4)

Scientists experiment with using viruses to combat antibiotic-resistant bacteria. Recently, Northwestern University modified DNA from a bacteriophage, a virus that attacks bacteria, to combat Pseudomonas aeruginosa. Pseudomonas aeruginosa is the leading cause of hospital infections, a highly antibiotic resistant bacteria, responsible for 3,000,000 cases in the US annually, and 35,000 deaths. These infections are expected to increase as bacteria continue to develop new ways to resist antibiotics.

The experimenters used electroporation - short, high-voltage pulses of electricity - to poke holes in the bacteria's outer cell. The phage DNA then enters the bacteria through this stimulated “infection”. So far, these trials have been successful at eliminating the bacteria.

The idea of treatment without side effects - modifying viruses to attack specific bacteria - seems to be a much better alternative than current antibiotics used today that affect many different systems in the human body. Scientists are given much more incentive to explore this new field, as much is still unknown about phages, despite the existence of billions. As those at Northwestern University see it, the goal is to one day mass produce these modified phages as a therapeutic that will save billions.

Article: https://phys.org/news/2024-01-viruses-deadly-pathogens.html

- ES

California - What's Up with Your New COVID Policies? (ES - W3)

California and Oregon, once among the most cautionary of states during the early years of the COVID-19 pandemic, have declared radical policies countering current federal government guidelines. No longer are asymptomatic, infected individuals required to quarantine for 5 days (and mask up to day 10). Instead, those who test positive yet exhibit no symptoms are free to attend school, work, and travel. As Dr. Bronner, a medical practitioner for viral pathogens, puts, “The emergency has ended. Covid-19 is endemic.”

This is quite problematic. The determinant to whether someone quarantines should be based on transmissibility. Asymptomatic people are still capable of spreading the virus, and studies published by the JAMA Internal Medicine Network show that the highest contagious period occurs a few days before and after symptoms appear. Moreover, over 1,500 people still die each week from COVID. There also still remains the faulty federal guideline that only people who test positive have to quarantine. Those who don’t are under no obligation to isolate.

As epidemiologist Jason Salemi puts, “I don’t want people coming to work and interacting with me if they’ve got the flu and are still infectious, if they’ve got strep throat and they’re still infectious, and of course if they’ve got Covid-19 and they’re still infectious.” 

Surely, this statement is agreeable to many.

Yet, Oregon has had these policies implemented since May, and its death and hospitalization rates have remained similar to the national averages. 

Reasons for relaxation of COVID guidelines stems from the perspective that the benefits of long isolation no longer surpass the need for those in the workforce, school, or other life activities. This ties into the larger, collective feeling of exhaustion of Americans towards news of a virus that has been around for too long. In response to Dr. Bonner, the emergency response has ended… but the danger still exists.

Article:

https://www.nytimes.com/2024/01/21/us/covid-rules-california-oregon-cdc.html?campaign_id=9&emc=edit_nn_20240122&instance_id=113142&nl=the-morning&regi_id=222222685&segment_id=155973&te=1&user_id=179558523a1dc7fb048d340d9d11a24a

- ES

"Disease X" - The Next Devastating Pandemic (ES - W2)

In the ongoing World Economic Forum (WEF) in Davos, Switzerland, global leaders meet to discuss the world’s most pressing issues. Among the topics to be discussed is the threat of “Disease X”, the hypothetical virus that will be the world’s next devastating pandemic. Leaders are to assume it will be deadlier and more contagious than ever, and the WHO has already placed it on the priority list (alongside ongoing ravagers like COVID-19, Ebola, and Zika). It is hopeful that the forum will create an effective plan for quick emergency response. This might mean bolstering currently limited resources. As Dr Thomas Russo, an infectious diseases expert at the University of Buffalo Jacobs School of Medicine and Biomedical Sciences, puts, “…increased surveillance and biosecurity is needed as the world continues its use of live animal markets and deforestation.” The risks for another global pandemic unceasingly increase.

Article:

https://www.independent.co.uk/news/world/europe/next-pandemic-disease-x-b2479196.html

- ES

Unvaccination, COVID-19, and the Rise of Outbreaks (ES - W1)

Sars-CoV-2 is viewed by many as an unprecedented virological takeover whose global ends see no bounds. Its effects on future viruses, though, may be even more dangerous.

Fears of COVID and infection, hospital overloads, quarantines, a growing anti-vaccine movement, and declining trust in governmental and nongovernmental health organizations alike have resulted in close to 85 million children under-immunized and 60 million “zero-dosed”. Under-immunized meaning kids who didn’t finish their shot series, and “zero-dose” those who still have not yet received any of the standard vaccinations given during youth, on track to age out of these routine immunization programs. Countries requiring the most urgent response include, but are not limited to: Nigeria, Ethiopia, India, the Democratic Republic of Congo and Pakistan.

We are beginning to see how the lack of vaccination is affecting the globe. 22 million children in 2021 missed the vaccine for measles, with an additional 13.3 million not receiving the second dose. Measles rose 43% 2022. Now, 47 countries have serious measles outbreaks (compared to 16 in 2020). The WHO and CDC predict 2023 will be twice that. Additionally, Nigeria has the largest diphtheria outbreak ever (for the country), and twelve countries, including Afghanistan, Zimbabwe, are suffering from the polio virus.

“Zero-dose children” make up 50% of child deaths from illnesses preventable by vaccine. While some countries have higher vaccination levels post-COVID, others are in dire need of aid.

Article: https://www.nytimes.com/2023/11/25/health/vaccines-children-zero-dose.html?campaign_id=9&emc=edit_nn_20231126&instance_id=108628&nl=the-morning&regi_id=222222685&segment_id=151002&te=1&user_id=179558523a1dc7fb048d340d9d11a24a

- ES