Thursday, November 14, 2019

A New Way to Control Virus Vectors: Stimulating the Arthropod Immune System

Viral diseases spread by an arthropod vector are exceedingly difficult to control and counter. In a recently published study, researchers at Washington State University discovered a new way to control viral proliferation within arthropod vectors - by stimulating the immune system. Using genetic screening, they discovered an insulin-like receptor that is part of the arbovirus immune system. When stimulated, the receptor activates the JAK/STAT pathway - a key component of the antiviral innate immune response. With increased JAK/STAT activation, the arthropods demonstrated enhanced ability to prevent viral replication. The researchers started by looking at West Nile in fruit flies, and once that proved successful, they studied the effects of insulin on mosquitoes and found that it suppressed West Nile, Zika and dengue. This research has tremendous implications on the prevention of virulent ARBO diseases Most notably, deadly flaviviruses such as West Nile, Dengue and Zika are all spread by arthropods. Because there is no ‘cure’ for any of these diseases, prevention is the best/only way to limit casualties. Mosquito populations have proven difficult to control, necessitating alternative methods of limiting the spread of viral diseases. 
~ Avi Kaye
Article: Ahlers, L., Trammel, C., Carrell, G. et al. Insulin Potentiates JAK/STAT Signaling to Broadly Inhibit Flavivirus Replication in Insect Vectors. Cell Reports, 2019: 29(7): 1946-1960. 

Thursday, November 7, 2019

Solving Reo Transcription One Discovery at a Time

There is still much to learn about the activity of Reoviridae - our “weirdo” segmented dsRNA family. The viral family uses encapsidated RdRp's to tightly regulate transitions between transcription and genome replication, both of which must be completed in the viral life cycle. A recently published article that conformation changes within enzymes and RNA “trajectories” support different transcriptional states and lead to an ‘ouroborous’ or circular model of genome replication that solves an equivalent of the ‘tip problem.’ Using cryo-EM structures, the researchers were able to visualize several distinct RdRp conformations including an ‘initiation’ state when interacting with the RNA replication fork, an elongation state that forms a transcription bubble, and an abortive state when releasing from the RNA. The shape and interactions within these conformations are consistent with a unique transcription technique within the cytoplasmic viral factories where each viral segment associates with a dedicated RdRp and minus strands are constantly recycled for both transcription and replication. It also offers mechanisms for regulating switches between transcription of viral mRNA and complete genome replication since an ‘abortive’ and ‘initiating’ RdRp can be found on the same particle. A criticism of the paper is that the authors only looked at canine parvovirus, potentially limiting generalizability, however the researchers are confident that the principles are conserved across reoviridae. 

~Avi Kaye

Article: Ogden, K. Reoviridae transcription is more than an open-and-shut case. Nature Structural and Molecular Biology, 2019. .

Tuesday, November 5, 2019

Fluzone Completes Transition from Trivalent to Quadrivalent Vaccine After Latest FDA Approval

The FDA approved the high-dose quadrivalent influenza vaccine Fluzone (Sanofi) for adults 65 and older earlier today, completing Fluzone's transition from a trivalent to a quadrivalent vaccine [1]

This quadrivalent version of Fluzone contains 2 influenza A and 2 influenza B strains: H1N1, H3N2, Victoria lineage, and Yamagata lineage. All strains are inactivated. With this new approval, Fluzone is now indicated for use in individuals 6 months and older. Contraindications include patients with a history of anaphylactic reactions to any component of the vaccine. Individuals with a history of Guillain-Barre after influenza vaccines should be evaluated on a case by case basis. Immunocompromised patients may still receive Fluzone, but immune response will likely be reduced [2].

This quadrivalent vaccine will be available at the start of next (2020-2021) influenza season, while the trivalent vaccine is currently available [1].

Jacob Thoenen

1. FDA OKs Fluzone High-Dose Quadrivalent Influenza Vaccine for Older Adults
2. Fluzone Quadrivalent Prescribing Information

Monday, November 4, 2019

Bats can infect humans?

Found this super interesting article which claims that there is viral spillover between bats and humans, and evidence of this has been found in India. This usually happens through what is called "bat hunting" and bats biting humans in an effort to get away from them. Seems like a pretty avoidable thing to me.


Abhinav Singh

Universal Flu Vaccine?

I found this article super interesting. The prospect of having a universal flu vaccine is relatively foreign and by looking at the pathway of flu development (and targeting flu development proteins), a vaccine may be developed that serves this purpose. Testing the antibody that was discovered in humans in the future should lead to some pretty interesting results.

-Abhinav Singh

Sunday, November 3, 2019

The lasting immunological implications of measles

Two recent studies published on October 24., 2019 reveal that although patients, specifically children, can recover after measles diagnosis, lasting immunological implications can occur making children susceptible to other infections such as influenza and pneumonia years after initial infection. [1] This phenomena is due to "immune amnesia" which involves the measles virus wiping out about 11% to 73% of protective antibodies within children infected with the virus and even further the measles virus has been shown to wipe out most memory cells within infected children who hadn't been vaccinated. [2] Given its widespread and long-lasting implications, this recent discovery has underscored the importance of patients, specifically children, to receive an MMR vaccine. [2]



CRISPR as an antibiotic?

CRISPR has often been used to solved macroscopic tasks such as genetically altering mosquitoes in order to prevent the spread of malaria, curing some patients of certain diseases such as a common blood disorder: sickle cell disease, or helping to genetically engineer certain crops such as tomatoes for commercial benefit. However, it is recently being thought of as a solution to help address common issues among viruses including antibiotic resistance. A common problem among viruses is their innately rapid ability to replicate and adapt. A recent study conducted by Dr. David Edgell was able to utilize Cas9 (a CRISPR associated enzyme) in order to target a species of Salmonella by forcing it to make lethal cuts in its genome. Although it will still take a relatively long time in order to commercialize a CRISPR, therapeutic drug, recent studies have shown promise in the ability to target specific bacteria and viruses attacking our immune system.