miRNAs Have Such Rock Star Status That Real Rock Stars Write About Them

Tonight I went to a concert in which the two bands I went to see were fronted by biologists: Bad Religion (Greg Graffin Ph.D) and Offspring ("Dexter" Holland soon to be Ph.D). 

I go curious as to what they've been publishing in the biomedical literature and found a cool paper published during 2013 in PLoS ONE whose first author is Bryan Holland of Offspring.

I read the paper and it is fascinating. 

The subject of the paper is the phenomenon of miRNA's. These are non-coding (i.e. non-protein making) short pieces of RNA that function to regulate genes. What Holland's paper focuses is on  is miRNA's within the genome of HIV.  The paper argues that 8 miRNA like sequences found in HIV may bind to cellular targets and be responsible for dysregulation of cellular genes. This dysregulation may play a role in HIV's ability to evade host defense, something it does quite readily.

I find the whole topic of RNA fascinating because as the myriad functions of RNA (tRNA, ribozymes, RNAi, miRNA, siRNAs, snRNPs, etc) are detailed it is clear how versatile this molecule is giving a lot of validity that our modern DNA world evolved from an RNA one.

Ebola: Will it Find the US as Inhospitable as Lassa Fever Did?

While the press is speculating on the ability of the Ebola virus to be imported into the US--a fear heightened by the infection of two Americans--I think it is important to remember that Lassa Fever, Ebola's fellow traveler, has trod this ground before. 

Lassa Fever is a hemorrhagic fever endemic in West Africa and spread via rodent urine and through body fluids. It kills about 5000 people yearly in Africa and, although death is rare, it serves as a prototype of what to do with imported Ebola cases. Bottom line: situational awareness coupled with strict infection control.

Recent Lassa importations occurred in New Jersey in 2004, my home of Pennsylvania in 2010, and Minnesota in 2014. In total, approximately 7 cases of Lassa Fever have been identified in travelers in the US. In all cases, no symptomatic secondary transmission were identified. 

While Ebola is a horrific disease and a serious concern in Africa, should it make itself to the US in a traveler incubating the virus, it will find the US as inhospitable as its weaker fellow gang member, Lassa Fever, has repeatedly learned.

HIV & The Will (or its absence) to Live

Although I primarily practice infectious diseases and critical care medicine, I am also trained and board-certified in emergency medicine. To keep somewhat active in the field, I work about one shift per month in an emergency department (ED). I don't often have my infectious disease world intrude into the ED, but yesterday it did. 

I was involved in the care of a AIDS patient with toxoplasmosis who came to the ED for an unrelated reason. However, the infectious disease issue soon supplanted the original reason for the visit. 

Toxoplasmosis occurs in AIDS patients who are severely immunosuppressed. This opportunistic infection, which is treatable, was much more common in earlier eras in which individuals with HIV had no effective treatments. In the modern era, in those who have access to medications, it is quite rare. In my ID fellowship, I think I only saw one case in an individual newly diagnosed with HIV. 

Yesterday's case wasn't like that--this person had willfully stopped taking anti-retrovirals and anti-toxoplasmosis medications. 

I found the entire experience frustrating as I, like many other physicians before me, was futile in  persuading the patient that without treatment death would soon occur. 

As I've learned by myriad interactions with individuals recalcitrant to complying with treatment recommendations, a fundamental choice to live has to be the precondition for anything anyone says to matter.

If Zombies Taught Epidemiology

Many people who are interested in the spread of infectious diseases have co-opted the zombie craze in order to emphasize key preparedness messages that are "common" to both, including the  CDC (I even have a CDC zombie hunter shirt).

One of the best known popular culture items in this social phenomena is the novel and movie World War Z which depicts an outbreak of an unknown infection that turns individuals into rabid zombies. There are many epidemiological points made in the movie but the one that I want to focus on regards who is susceptible to infection and who is immune. 

This is a major question in any outbreak and, just as in World War Z, figuring out the reason why is often a game-changing discovery. For example, in HIV there is a well known mutation that a portion of the populate harbors in CCR5, HIV's co-receptor, that can render one unable to be infected (see The Berlin patient). In a similar fashion, sickle cell trait confers resistance to malaria. 

In the case of HIV, understanding the role of the CCR5 co-receptor led not only to The Berlin Patient's path-breaking bone marrow transplant, but to the development of the drug mariviroc. Mariviroc blocks CCR5 thwarting the ability to the virus to infect cells and is a component of modern HIV drug cocktails.

So, in the early days of an outbreak understanding who is being spared is as important as understanding who is being infected--a little bit of zombie pedagogy. 

Chimeric Pathogens: Something for Everyone?

In the 2011 film Take This Waltz a character played by Michelle Williams "playfully" states to her husband (played by Seth Rogen): "I love you so much that I'm gonna inject your face with a curious combination of swine flu and ebola."  This crazy line prompted me to think about the topic of pathogenic chimeras--no surprise for someone looking for infectious diseases everywhere.

Interest in chimerical pathogens is understandably fascinating but something I find kind of puzzling because pathogens on their own are usually sufficiently deadly. 

However there has been genuine interest in chimerical pathogens proving that this is not a phenomenon just restricted to fiction. For example, the former Soviet Union's bioweapons program (the existence of which was recently denied by Putin decades after Yeltsin admitted its existence) attempted to develop combinations of pathogens such as Venezulean Equine Encephalitis Virus and Vaccinia, possibly for vaccine  and/or virulence increasing offensive purposes. There are also sorts of rumors about chimeras involving Ebola and Smallpox.

The line also made me think about the fact that chimerical pathogens aren't solely the result of human ingenuity and genetic engineering, as many chimeras exist in nature.  A few important chimeras occur in nature. Some important examples of natural chimeras include:

• Influenza viruses that are the result of gene swapping between avian, human, and swine strains
• Toxigenic strains of Cornyebacterium diphtheriae, the bacteria that causes diphtheria, which are infected by a bacteriophage that elaborates the namesake toxin prompting symptoms
• E.coli O157:H7, as it elaborates a toxin derived from Shigella bacteria

Also, bacterial strains such as vancomycin-resistant Staphylococcus aureus are also chimeric in that they gain antibiotic resistance by acquiring the requisite genes from vancomycin-resistant enterococci.

Genetic information is transferrable so it should be no surprise that chimeras are a part of nature. Indeed, they sort of exemplify the malleability inherent in evolutionary biology.

Thinking about the topic more broadly, chimeras of all sorts capture people's imaginations. Perhaps its natural to want to create or have enhanced versions of everything? For example, the uppercut of Mike Tyson coupled to the footwork of Mohammed Ali; the guitar skills of Eddie Van Halen and Angus Young in one person; or, one of my childhood favorites, Serpentor.