Sunday, January 29, 2017

HCV Linked to Multiple Cancers Besides Liver Cancer.

Hepatitis C virus (HCV) infection has been established as a risk factor for hepatocellular carcinoma, the most common type of primary liver cancer. However, a study recently published in Cancer found that HCV infection is associated with a number of other cancers as well.

This was a case-control study using data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. 1.6 M cancer cases were matched to 200,000 cancer-free controls. HCV prevalence was higher in cases than controls (0.7% vs 0.5%). HCV was positively associated with cancers of the liver, intrahepatic bile duct, extrahepatic bile duct, pancreas, and anus; nonmelanoma nonepithelial skin cancer; myelodysplastic syndrome; and diffuse large B-cell lymphoma. Specific skin cancers associated with HCV were Merkel cell carcinoma and appendageal skin cancers. It was negatively associated with uterine cancer and prostate cancer.

However, it is thought that the association between HCV and anal cancer and nonepithelial skin cancers may be confounded by shared risk factors. A high prevalence of HCV infection is seen in men who have sex with men and injection drug users; both groups have a high prevalence of HIV infection, which is associated with increased risk of anal cancer. HIV infection is also associated with an increased risk of nonepithelial skin cancers.

The authors suggested that HCV was negatively correlated with uterine cancer because total abdominal hysterectomy is associated with a risk of hemorrhage requiring blood transfusion, and the blood supply was not screened for HCV before 1992. Therefore, the prevalence of HCV would be higher in patients with uterine cancer, who obviously did not previously undergo hysterectomy.

HCV is thought to be negatively associated with prostate cancer because of lower rates of screening for prostate cancer in HCV infected patients, who are often of lower socioeconomic status.

-Sally Tran

Huseman A. "Study shows link between Hepatitis C virus, multiple cancers." Baylor College of Medicine News. 2017 Jan 26.

Mahale P, Torres HA, Kramer JR, Hwang L, Li R, Brown EL, Engels EA. "Hepatitis C infection and the risk of cancer among elderly US adults: A registry-based case-control study." Cancer. 2017 Jan 24. doi: 10.1002/cncr.30559

Saturday, January 28, 2017

Uganda faces an avian influenza outbreak

Uganda recently reported an outbreak of bird flu and is taken extra precautions to avoid a transmission to humans. There were hundreds of birds that were found dead around the shores of Lake Victoria, which caused the health officials and leaders in Uganda and even Kenya to go on high alert.

As we know, there are a number of different forms of influenza that can get into birds and humans. Obviously some strains are more dangerous than others and this form of bird influenza appears to be very deadly. With birds, the influenza is typically caused by influenza A viruses, which are classified/names by their proteins of hemagglutinin (H) and neuraminidase (N).

While avian influenza will typically not make its way to infecting humans, transmission is a possibility and that is why Uganda leaders are very cautious at the moment. Direct contact with a bird that is exposed to the virus or even indirect contact could lead to human infection and that can then lead to human-human transmission. So far there have luckily been no human cases reported. Let us hope no cases arise!

-Jeanette Rios (‘18)

Thursday, January 26, 2017

The concept of One Health

One interesting way of seeking to solve interconnected world epidemics has been through the One Health Concept. This concept is “increasingly integrating human medicine, animal health, and environmental science to prevent and treat… serious public health threats.”

The Defense Health Agency’s Public Health Division is using this concept, to target influenza. Influenza, as we know, is part of the Orthomyxoviridae family and is a negative sense, segmented virus. It has four flu virus types A-D, with A and B causing the largest proportion of human disease. Due to the segmented nature, the nature of RNA viruses, and other genetic variation techniques, the influenza virus is rapidly evolving – often enough to cause a pandemic.

Since birds are one of the more important reservoirs of influenza viruses, it brings up the importance of animal health and its impact on human health. One strategy that was implemented was the “stamping out” strategy. This in turn could lead to infection of the humans leading the elimination of the disease. Further, it also causes financial challenges through overall cost-effective analysis. One example of that was the $4000 million lost to the economy due to the “swine flu” epidemic.

The best way to help propagate the One Health concept, which has been endorsed by more than 850 prominent scientists, is through yearly immunization. One interesting point was that of Skerrett, “If you get immunized while you’re pregnant, you will transfer some protection to your unborn child. And, getting immunized protects those around you who cannot receive the vaccine.”

Gianna Nino-Tapias ('18)

Orose C. One Health concept highlights collaboration as key to preventing and fighting disease. Defense Health Agency Immunization Healthcare Branch. 24 January 2017.

Wednesday, January 25, 2017

Rotavirus & Its Effect on Interferon Production

New research on rotavirus infection shows that rotaviruses may alter the epithelial’s immune response to evade the immune system.  They do this by altering the expression and presence of interferon (IFN I & III), cytokines that act as the body’s antivirals, in the intestinal epithelium.  When live rotavirus is introduced to culture (called a human intestinal enteroid - HIE - that, for the most part, acts like a normal functioning intestine), IFN I was not produced and neither was IFN III even though the genes expressing IFN III were functioning.  But, when inactivated virus was introduced IFN III was produced normally and could be found in the culture.  What this suggests is that rotavirus in some way inhibits IFN I and the translation of IFN III.  Furthermore, the researchers found that by “Adding type I IFN to the HIE cultures with live rotavirus [it] reduced viral replication more efficiently than adding type III IFN.”  

- Devon

Sunday, January 22, 2017

Endogenous Retroviruses and Neural Gene Expression

Endogenous Retroviruses (ERVs/retrotransposons) are a class of transposons which exhibit great similarity to and, in some cases, are derived from retroviruses. ERVs have long been known to be components of eukaryotic genomes, and, in many cases, have persisted in those genomes for millennia, and in humans, these components make around up 10% of the total genome, though they are largely found in non-coding regions of the genome.

Researchers at Sweden's Lund University have determined that some ERVs serve as "docking platforms" for TRIM28, a protein which halts the transcription of ERVs as well as coding sequences to which they are adjacent. That known genomic regulators of the central dogma only compose 2% of the human genome, a fifth of the extent to which ERVS are represented, and that ERVs are transposable in the genome might indicate that this regulation might have far-reaching effects on human gene expression and, potentially, behavior and evolution as well. Another curious aspect of this research to consider is that many ERVs with potential roles in regulating the development of the human CNS are not found in our closest primate relatives, and thus may shed particular light on the differences which may exist between our brains, their development and their evolution.
Per Ludvik Brattås, Marie E. Jönsson, Liana Fasching, Jenny Nelander Wahlestedt, Mansoureh Shahsavani, Ronny Falk, Anna Falk, Patric Jern, Malin Parmar, Johan Jakobsson. TRIM28 Controls a Gene Regulatory Network Based on Endogenous Retroviruses in Human Neural Progenitor Cells. Cell Reports, 2017; 18 (1): 1 DOI: 10.1016/j.celrep.2016.12.010


Enteroviruses may be linked to increased type I diabetes risk

Researchers in Finland are contributing to a growing body of literature that suggests that enterovirus infections may be one of several environmental triggers that cause type I diabetes. Their study showed that children who were in the early stages of type I diabetes had a more remarkable history for enterovirus infection than control children in the past year. The study sample was composed of 129 children with multiple islet autoantibodies and 282 children without autoantibodies. Scientists tested several stool samples from children in both groups. They noted that the enterovirus infections occurred more than a year before the islet autoantibodies developed, which may indicate the time required for an enterovirus to elicit an autoimmune response of the pancreas in genetically susceptible individuals.

I was skeptical of this finding since enterovirus infection is extremely common and yet type I diabetes has a prevalence of 0.4% in the US. So, I looked up an article in Pub Med Central that reported the history of association between enterovirus and type 1 diabetes. Apparently, this association has been around since the 1960s when Gamble et al reported seasonal incidence of type I diabetes that paralleled enterovirus infection. Experiments on mouse models do seem to provide compelling evidence of a causal link. Several research groups have conducted serological and RT-PCR studies on people with type I diabetes that reveal more enterovirus antibodies and RNA. Since the majority of these studies are retrospective, they cannot determine causality. Ultimately, the connection between enterovirus infection and type I diabetes is weak.


Dengue-Resistant Mosquitoes?

Researchers at Johns Hopkins University recently engineered dengue-resistant mosquitoes that might be useful in the effort against the disease. The mosquitoes were engineered to curtail completely their ability to transmit dengue virus to humans.

The mosquitoes used in the study (A. aegypti) had their genes altered to code for "Hop" and "Dome" proteins which would activate the JAK/SAT antiviral pathway. This pathway then limits the ability of Dengue viruses in those mosquitoes to proliferate, and, crucially, prevents their movement to mosquito salivary glands. These genetically engineered mosquitoes also produce fewer eggs than do wild type mosquitoes.

The impact of this research could be tremendous. The release of dengue-resistant mosquitoes into nature, in places where Dengue is endemic, would introduce that resistance to the mosquito gene pools in the area and could significantly reduce Dengue transmission and infection. This is furthered by the effects of the gene therapy to limit the reproductive potential of the mosquitoes. That this approach may also seem more 'humane' than the release of sterile insects, or the killing of insects using pesticides, also adds to its appeal.
Jupatanakul, Natapong, et al. "Engineered Aedes aegypti JAK/STAT Pathway-Mediated Immunity to Dengue Virus." PLOS Neglected Tropical Diseases11.1 (2017): e0005187.

-Muzz Shittu

A new potential genital herpes vaccine

Scientists have been trying to develop a herpes simplex 2 vaccine for nearly 40 years with little success. Now, the search for an effective genital herpes vaccine may be almost over. A study published in PLOS Pathogens on January 19, 2017 reported promising results for a herpes simplex virus 2 trivalent vaccine in animal models. The vaccine uses a novel strategy that induces two antibodies that prevent the virus from evading the immune system and one antibody that blocks cell entry. The vaccine was created by researchers in University of Pennsylvania School of Medicine’s Institute for Immunology. Data show 4 of 6 monkeys had robust antibody titers and 98% efficacy in guinea pigs. The vaccine developers are looking for pharmaceutical companies who may be interested in further developing the vaccine and testing it in humans. Human trials can begin as soon as 18 months once a pharmaceutical company is found.

This vaccine could have tremendous impact on human health. Nearly 500,000,000 people worldwide are living with herpes simplex 2 virus. In the United States, 1 in 6 people have genital herpes.


Updates in Zika Research: Potential Drug Found

The Zika outbreak has been under constant scrutiny for nearly two years now (beginning with the Brazil epidemic in early 2015). Thankfully, the WHO announced the end of the Zika epidemic in 2016, but researchers are still hard at work finding specific therapeutics to battle this virus that has potentially to lead to severe consequences.

This week, Rausch et al. published a paper in Cell Reports identifying a panel of small molecules that seem to inhibit Zika entry into cells. The group, led by Sara Cherry, PhD, at the University of Pennsylvania, screened over 2000 bioactive molecules using high-throughput screening technology and identified 38 promising candidates. From there, they picked nanchangmycin as the most promising candidate. It seems to disrupt clathrin-mediated endocytosis.

Other related flaviviruses and non-flaviviruses, such as West Nile, dengue, and chikungunya, also use a similar method for cell entry. Nanchangmycin seems to also disrupt their ability to infect cells, so this research represents the beginning of potentially a new class of antivirals.

News Article:

Published Research Article:

-- Sharon Kam