VITN Blog Post #2: New Technique Provides Insight into how RNA Viruses Interact with our Cells

Researchers at Cambridge University were recently able to develop a method to better understand how Zika virus RNA is able to infect human cells. What’s more exciting about this discovery, is that the researchers say their method, called COMRADES (Crosslink of Matched RNAs and Deep Sequencing), is universally applicable to all RNA viruses in any host cell. When an RNA virus infiltrates a cell, viral replication usually takes place in the cytoplasm of the infected cell. Strands of human RNA float around in the cytoplasm and when human RNA runs into viral RNA, the two molecules can undergo RNA base pairing where their complementary base pairs can bind to each other - Uracil to Adenine, and Cytosine to Guanine. This essentially has the effect of “zipping” the two molecules together.

Prior to this research, little was known about the specificity of this process and the details on how and where on the RNA strands this occurs. COMRADES gives scientists the ability to better understand this process and opens the door for development of methods to interfere with this part of the infection process. Using COMRADES, the positioning and identity of every base pair involved in this zipping can be determined.  

RNA viruses are thought to be highly dangerous specifically because of their extremely high mutability rates. The tool utilized by most RNA viruses for replication, RNA dependent RNA polymerase, has no system for proofreading newly transcribed strands of RNA. If there is one type of virus that might be able to trigger a world-wide pandemic, it is likely a strain that hasn’t yet evolved but eventually will evolve from an RNA virus. COMRADES takes us another step closer to understanding these fascinating microbes and another step closer to preventing such a pandemic.

News Article: https://www.sciencedaily.com/releases/2018/09/180910111255.htm

Source Article: https://www.nature.com/articles/s41592-018-0121-0

- Renata Starbird

VITN post no.3- "New HIV diagnoses across the UK fell by 17 per cent in 2017"

Public Health England (PHE, England's answer to the CDC) recently published an article stating that new HIV diagnoses have fallen for the second year in a row, by 17% in 2017; on parr with that of the new HIV diagnoses back in 2000- surely a great leap forward.

The decline has been reportedly driven by gay and bisexual men due to the relatively-new culture of STI testing available for free on the NHS in the UK, as well as an increased uptake in anti-retrovirals.

Another group contributing significantly to the decrease in new cases is the black African and Caribbean community, for whom new cases among heterosexuals has been steadily decreasing over the last 10 years.

Steve Brine, public health minister said that we're "well on our way to eradicating it (HIV) once and for all, but we have not an ounce of complacency." An important stance to take on diseases as life-changing as HIV/AIDS.

This article raises two questions for me, as a young brit;
-at what stage does the cost of screening outweigh the benefit and are we anywhere near that point?
-should countries like the US be looking towards other countries as case studies for a) mass-screening and treatment, and ultimately, as case studies for NHS-like services, given increased coverage and efficacy?

PHE is working to "control" HIV by 2030, and any sign of decreasing new diagnoses is a step in the right direction. (Although the word "control" is vague and problematic to me personally.)

-Jack Whitehead 

VITN post no.2- "Bats spread Ebola because they've evolved not to fight viruses"

Having heard a lot about bats as reservoir hosts recently, I decided to read up more about them. I then fell upon a short, interesting new scientist article with the same title as above.

The article suggests that bats "provide a refuge" for some of the most deadly viruses because flying is very energy-demanding.
The article talks about viruses hijacking the cell machinery, as we know they do, to replicate their genetic material, but this leads to the production of very reactive free radicals during exercise, which can damage and fragment DNA.

Normally, if cells detect free DNA, it is interpreted as an emerging viral threat, and the molecule which coordinates response is "STING" (STimulator of INterferon Genes aka. transmembrane protein 173) which coordinates interferon production. However in bats, it was found that one serine residue was deleted, modifying bats' response to viral infections and leading them to tolerate infections other mammals would fight off, thus wild bats are capable of tolerating viruses for a long time at a low level.

The article states rightly that it is paramount that we understand the mechanism bats use to remain unaffected (but infected.)

Photo: https://www.sciencedirect.com/science/article/pii/S1931312818300416?via%3Dihub
1- The figure shows that STING-dependent IFN activation is dampened in bats, and this is due to an otherwise conserved serine residue being replaced, but reversing this mutation restores "normal" IFN activation and viral inhibition

-Jack Whitehead

VITN post no.1- The work of the CDC on the ground in Sierra Leone

Listening to Dr. Tai-Ho Chen recall his time spent in Africa, working for the CDC with Ebola, I was wondering what was actually done to be culturally-sensitive in a place where medicine is predominantly governed by spiritual healers and "witch doctors." Surely enough, I found a CDC article on "Improving Burial Practices and Cemetery Management During an Ebola virus Disease Epidemic- Sierra Leone, 2014."
The article documents the work of the CDC in being receptive to cultural practices whilst striving to mitigate ebola transmission in a very delicate part of life- death.

Ebola is mainly transmitted by physical contact with an infected person or their bodily fluids. Transmission is especially dangerous in the later stages of illness and death, and this is an issue in Western Africa, as cultural policies dictate touching and washing of the deceased- a prime route for ebola transmission.

The CDC assessed burial practices, cemetery management and adherence to recommended practices by directly observing burial ceremonies to assess the risk of transmission and to come up with a comprehensive burial plan which a) mitigated the risk of transmission whilst b) was receptive to the social and spiritual needs of the community.

The primary assessment showed that burials often took place in mass unmarked graves, and that community burials were more widely accepted, as this allowed the community more involvement and offered more transparency.

Namely with the help of the UK government, a burial team command centre was established in the west of the country (near the most densely-populated areas) to coordinate safe burials.

The preliminary assessment carried out by the CDC found that deaths were not always reported, testing for Ebola wasn't always carried out (even when recommended), decontamination of homes where ebola was present was not always carried out properly, and not all bodies were collected by burial teams, with multiple instances of bodies being hauled off in the back of trucks in unidentified burial bags to be placed in unmarked graves recorded, as well as examples of undignified burials whereby proper religious practices were not followed or families not allowed to observe the ceremonies.

It is easy to see how civilians were discouraged from reporting deaths, due to ebola or not, for fear of undignified burial ceremonies, and this was a crucial catalyst in the outbreak, as it encouraged further transmission of ebola.

From this case study, lessons must be learned about social and cultural sensitivity, as cause and effect analysis shows that a disregard for said practices will only make people turn to dealing with burials themselves; exacerbating an already deadly situation.)

Photos: https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6401a6.htm
1- A burial team preparing to collect another dead body for transport in the back of a truck
2- Unmarked graves in an ebola burial section of a cemetery
3- Dead bodies, personal protective equipment and medical waste buried together

-Jack Whitehead

VITN Blog #3: Monkeypox: UK's First Case of Rare Viral Infection confirmed

Monkeypox, which is a part of the orthopoxvirus genus and poxviridae family, was first observed in a group of monkeys in the late 1950s. About ten years later in the Democratic Republic of Congo (formerly Zaire), the first case of Monkeypox was recorded in humans. Since then, the disease has mostly stayed in western and central African countries. According the Center for Disease Control and Prevention (CDC), the viral infection begins with symptoms including backaches, swollen lymph nodes, and fever. Closely following the fever is a rash which usually begins on the face before spreading to other parts of the infected person’s body. Monkeypox has shown to be deadly in about 10% of all reported cases. African rodents are considered the main carriers of the disease, and human-to-human transmission requires direct contact. Recently, a Nigerian naval officer who traveled to the U.K. for training was found to be infected by Monkeypox. According to the Telegraph (an English tabloid), the infected man is likely to have contracted the disease in Nigeria where there is an ongoing outbreak of Monkeypox. English health officials estimate that more than 50 people could have been exposed to the viral disease.

(Check out the full story here: https://www.telegraph.co.uk/news/2018/09/08/50-people-could-have-exposed-rare-viral-infection-uks-first/)

-Ezra Yoseph

VITN Blog #2: South Korean Man Infected by MERS Virus, First Case in 3 Years

Middle East Respiratory Syndrome (MERS) is a viral respiratory disease that is caused by a novel coronavirus. Symptoms of the disease can include fever, shortness of breath, and assorted gastrointestinal problems. The disease has been fatal in about 33% of all reported cases. Unfortunately for many people with the disease, one can present as asymptomatic and still have MERS. The respiratory infection is thought to be carried by camels, while most human carriers spread the disease in a clinical setting. The disease was first observed in Saudi Arabia, hence the ‘Middle East’ portion of its name. Since it first seen in 2012, MERS has been documented in approximately 2200 people in 27 countries. The most recent outbreak of MERS occurred September 6th, 2018 in South Korea. According to Korea Center for Disease Control (KCDC), the 61-year-old infected man contracted the disease during his business trip to Kuwait. So far, KCDC authorities have quarantined 20 people the man has come in contact with. Officials in Korea are doing everything in their power to make sure the outbreak does not do as much as harm as it did last time in 2015 when its exposure lead to 38 fatalities.


(Check out the full story here: https://www.channelnewsasia.com/news/health/south-korean-man-infected-by-mers-virus-first-case-in-3-years-10697648)

-Ezra Yoseph

VITN Blog Post #3 Cryo-EM helping gene therapy

Further to my last blog post, mentioning advances in spectroscopic techniques aiding our understanding of virology, this post is of great interest. Cyro-EM is a nobel prize winning molecular imaging technique that is transforming our knowledge of molecular structure. Here researchers have tried several different procedures to create detailed images of AAV2. This virus has applications as a vector in gene therapy and is therefore of importance. Understanding structure means understanding how they infect their target cells and evade the immune response. Such things are necessary for efficient delivery of genetic material to faulty host cells. Link below.

Miles Graham

https://www.sciencedaily.com/releases/2018/09/180907091503.htm