Tuesday, October 25, 2016

Bird Flu Blues in Delhi

There is growing concern in New Delhi as more birds are found dead after an outbreak of H5N1 (avian flu) killed several birds at the local zoo in early October.   Citizens fear that the flu is spreading beyond the walls and into the rest of the city and unfortunately it seems as though these fears are well founded. Since October 21, at least 10 birds have been found dead around the city, and since the zoo closed there have been reported deaths from a local migratory bird sanctuary.

H5N1 is a zoonic subtype of Influenza A of the orthomyxoviridae family. Although humans are not the primary host of the virus, experts agree that it would only take a few mutations for a highly virulent strain to emerge. Despite inefficient transmission, tpuoltry workers are at moderate risk for contracting the illness. Beginning symptoms include high fever, diarrhea, sore throat, and abdominal pain, but these can worsen and lead to respiratory distress or pneumonia. The current Asian strain has a mortality rate of about 60%. 

In response to the outbreak, the government is advising citizens to stay away from all bird carcasses for the time being, and has provided a hotline for people to report dead birds. Additionally, there are government response teams throughout the city to keep things clean, especially near poultry farms. At this time the state has issued reassurances that there is no reason to panic, and there is no ban on cooked poultry. Nevertheless, officials say they have stocks of Tamiflu tablets should the virus begin to infect humans.

 For more information see:

Elisa Hofmeister  '18

viral detection of bacteria (in food?)

Researchers at Purdue University have engineered a bacteriophage to detect strains of E. Coli in food. The phage targets E. coli O157:H7, a strain of the bacteria which causes food poisoning, kindey failure and death (through its secretion of the lethal Shiga toxin, one of the most toxic to humans).

The virus was engineered to induce luciferase expression in the cells it infects, causing the microbes to emit light. The virus was engineered for rapid diagnostic function, and produces detectable signals within just a few hours. This diagnostic method is cheaper than those which currently exist, and provides a modifiable template for the detection of other bacterial pathogens in food, such as Salmonella.
- Muzz Shittu

a whole load of letters: CRISPR/Cas9 and HIV

There's a powerful new weapon in the fight against HIV.
You guessed it.
It's CRISPR/Cas9.
Researchers at UCSF used the technique to create an array of CRISPR/Cas9 screens to variably knock out 45 specific genes in human T-cells in order to determine which of those hindered HIV infection. Genes that were determined as affecting the establishment of viral infection were involved in viral entry (the coreceptors for the CD4 receptor HIV exploits for entry, CCR5 and CXCR), and in the course of the viral life cycle after entry (the genes LEDGF and NUP153). The genes which relate to entry were found to have the greatest effect on infection.
Beyond the value these findings bring to the world of HIV research, they reinforce the use of CRISPR/Cas9 as a means to investigate host factors upon which viral courses of infection are dependent.

-Muzz Shittu

Viral Behavioural Change

Research conducted at Texas A&M may suggest a viral route to induce behavioural changes in mammals that may go as far as decreasing the urge to drink in cases of alcoholism. Researchers engineered a virus to deliver genes to D1 and D2 striatal neurons in mouse brains to inhibit striatal signals which promote drinking, and to enforce and restart signalling which limited drinking. The viral therapy successfully led to decreased alcohol consumption in the mice used for the study.


The end (then rebirth) of Polio in Nigeria

In September 2015, Nigeria, the last polio-endemic country in Africa, was declared by the WHO to be 'polio-free'. The country had not recorded a single new case of the disease in a year, fulfilling international requirements for removal from the polio-endemic list. This moment was seen as a historic public health achievement in the African context and in the global polio eradication effort.

Just a year later, however, this declaration was proven premature. At the time of the declaration, a significant part of the territory of North-East Nigeria's Borno state was controlled by the terrorist group, Boko Haram. By September 2016, however, the large majority of this territory had been reclaimed by the Nigerian government. With these military victories, though, came the end of Nigeria's polio-free status, as three cases of paralysis due to polio were found in territories previously occupied by Boko Haram. This illustrates the means through which social turmoil may contribute to viral emergence and reemergence.


-Muzz Shittu

2015-2016 Lassa Fever Outbreak in Nigeria

Between August 2015 and May 2016, Nigeria recorded 273 cases of, as well as 149 deaths from Lassa Fever. This outbreak was particularly significant both for its scope, with cases in 20 of Nigeria's 36 states, and for its greater-than-expected lethality. While Lassa infections commonly have mortality rates around 1%, and which climb to around 15% in extreme cases, the Nigerian outbreak saw a dearth rate over 50%, suggesting the emergence of a new, more lethal strain of the virus.

Many Nigerians have multiple and frequent points of exposure to and interaction with the rodent vectors which carry Lassa and other arenaviruses. Stores of grains and other foods may often be frequented by mice and rats, and, in some parts of the country, rodent meat is sold, eaten and makes up a significant portion of local diets. That the country is currently experiencing recession and significant tensions with regards to the nomadic cattle herders who produce much of the country's beef also contributes to pressures for other, more available sources of protein, increasing the risks of exposure to Lassa and similar zoonoses.

-Muzz Shittu

CRISPR in the fight against human viruses

The CRISPR/Cas system is naturally occurring in bacterial immune systems as a defense mechanism against virus attacks. Recent breakthroughs in CRISPR technology as an accessible, adaptable, and precise genetic engineering tool (using guide RNA to facilitate the degradation of specific nucleic acids) has found many potential applications to human diseases. 

The CRISPR immune system protects against viral attacks through three main steps: 
  1. Adaptation – DNA of the invading virus is incorporated into the CRISPR sequence
  2. Synthesis of CRISPR RNA –  The CRISPR sequence is transcribed to create small RNAs that function like a genetic GPS, guiding proteins (Cas9) to a specific target. 
  3. Targeting – A set of enzymes called Cas9 (CRISPR-associated protein) precisely cuts DNA and slices out invading viruses. 
CRISPR/Cas 9 has already been applied to four human viruses: HIV-1, Epstein-Barr virus, Hepatitis B virus, and Human Papillomaviruses HPV16 and HPV18. 

While there are still many barriers to overcome before application to the clinic will become reality, basic research studies in viral transduction with lentiviral or adenoviral vectors have been employed. In the future, scientists expect to see important clinical applications of this new gene-editing technology to treat viral infections, cancers, and genetic diseases. 

Source: White MK, Hu W, Khalili K. The CRISPR/Cas9 genome editing methodology as a weapon against human viruses. Discovery medicine. 2015;19(105):255-262. 

- Linda Shin