Saturday, September 24, 2016

Not another "zombie" virus (it's nothing to be scared of unless you are an amoeba)

Imaging of Mollivirus particles. (A) Scanning electron microscopy of two isolated particles showing the apex structure. (B) Transmission electron microscopy (TEM) imaging of an ultrathin section of an open particle after fusion of its internal lipid membrane with that of a phagosome. (C) Enlarged view of the viral tegument of a Mollivirus particle highlighting the layer made of a mesh of fibrils (black arrow), resembling Pandoraviruses’ intermediate layer, and the underneath internal membrane (white arrow). Three ∼25-nm interspaced rings are visible around the mature particle. (D) Light microscopy (Nomarski optics 63×) imaging of a lawn of Mollivirus particles, some of them (black arrow) exhibiting a depression at the apex. Figure via Legendre et al., 2016.

new study details the discovery of another giant DNA virus found in the Siberian permafrost. The new virus, called Mollivirus, is similar to another giant DNA virus that was also discovered in the permafrost, Pithovirus. However, although the pithovirus is oblong, the mollivirus is more round. It is also similar is structure to pandoraviruses, another set of large DNA virus. The mollivirus is smaller than some of the other large DNA viruses at 500-600 nm in diamter; however, it is still large enough to be seen with a light microscope (as seen by panel D in the picture above). Like the pithovirus, the researchers were able to infect an amoeba with the mollivirus and revive it. The genome is 651 kb long encoding for 523 proteins; 16% of the genes have their nearest orthologs to genes from pandoravirus and 10% to Acanthamoeba castellanii, most likely through horizontal gene transfer. As with these other large DNA viruses, most of the genes have no known orthologs. One of the more surprising findings is that ribosomes from the host are packaged into the virions. 

These large DNA viruses have changed the way we think about viruses. With genome sizes in these viruses ranging from 0.6 to 2.8 Mb, they are comparable in size to the smallest eukaryote parasites. Theses viruses have diverse morphologies as seen below. 

A Pithovirus. Credit: ulia Bartoli & Chantal Abergel; Information Génomique et Structurale, CNRS-AMU via Nature.

Marseillevirus at different stages of its formation in an amoeba.
Credit: Copyright Raoult / URMITE via Science Daily.

The complex interior of a Mimivirus. Electron microscopy at magnification of about 200.Credit: Didier Raoult, picture by N. Aldrovandi via Live Science.

Megavirus virion via Virology Blog.

Pandoravirus virion via Virology Blog.

Hopefully the reporting on the discovery of the mollivirus will be better than that of the pithovirus. When the pithovirus sample from Siberia was revived in amoebas, many science news sites proclaimed the scientists had resurrected a zombie virus and that unknown dangers lay in wait. The headlines from other news sources were much worse and I won't bother linking to them. Some news reports were much better and specifically mentioned that this virus posed no risk to humans. These viruses pose a risk to some organisms, but if you aren't an amoeba, then you'll be fine. These discoveries are offering vital clues into the evolution of viruses. Their discovery has also helped restart a conversation of if viruses are alive or not and what the definition of life should be. 

Tuesday, September 20, 2016

Zika: What does herpes have to do with it?

HSV-2 virus particle. (Courtesy of Linda M. Stannard, University of Cape Town) via Virology Online

New research has discovered an important risk factor for Zika virus crossing the placental barrier: co-infection with Herpes simplex virus-2 (HSV-2). In the study, the researchers used a first trimester trophoblast cell line that has been well characterized and infected it with two different strains of Zika virus and one of Yellow fever virus. The cells infected with Yellow fever virus survived despite the virus actively replicating whereas both strains of Zika induced apoptosis in infected cells. The researchers also discovered that infection with Zika inhibited the type I-β interferon pathway (a signaling protein that triggers an immune response against viral infection). Zika infection also interfered with trophoblast differentiation into spheroids (something that this cell line does under the right conditions). 

These are very important findings that help us understand the biology of Zika. It's when researchers tested Zika virus infection in cells already infected with HSV-2 that they found something very interesting. When the cells were infected with HSV-2, the expression of three receptors, required for flavivirus entry into cells, were increased. To test to see if this helps Zika virus cross the placental barrier, mice were infected with Zika virus in either a single infection or after prior HSV-2 infection. Zika viral RNA levels were low in the mice only infected with Zika; however, in  the mice previously infected with HSV-2, the Zika virus RNA titer was incredibly high. These results suggest that prior HSV-2 infection could aid Zika virus in crossing the placental barrier. 

The researchers tested HSV-2 infection because HSV-2 is prevalent in NE Brazil where microcephaly cases seem to be higher than in other places. The researchers hypothesize that the prevalence of HSV-2 in NE Brazil could help account for the increase in Zika-associated microcephaly cases there. Prior HSV-2 infection could be a risk factor that may make Zika infection worse in pregnant mothers, so these are very important findings. Hopefully researchers will investigate further with retrospective studies to see if there is an association here.  

Saturday, September 17, 2016

Zika update 9-17-16: TORCHZ, Culex and more

Aedes aegypti feeding. Via Arizona State University Biodesign Institute

It's been an interesting couple of weeks for Zika research and news. As always, there's been good and bad news. There has also been a huge development that I'm saving for last.

In Florida, the zone of local infection in Miami Beach has been increased by three times. The number of local transmission cases are up to 93 (or were at the time of the article). The area of local infection is likely to increase further. In Puerto Rico, the outbreak is continuing to grow and the number of confirmed cases have increased to almost 20,000. Because most cases are asymptomatic, the total number of cases is likely much higher and some are predicting that as many as 1 in 4 could be infected before the outbreak stops. It's disappointing that much of the news focus has been on Florida when Zika is causing outbreaks in US territories to a much larger extent.

Also reported is that Zika can be transmitted through bodily fluids. The CDC has released an initial report on a case from Utah where an elderly patient died from Zika infection. A relative of this patient contracted the virus without the normal transmission routes. It turns out that the titer of Zika in his blood was 100,000 times above normal, and likely passed the virus to his relative through normal exposure from personal care. The CDC has also officially announced that Zika can be transmitted by sexual contact with an infected male or female. They have also released a preliminary guideline for dealing with sexual transmission. Basically, use protection or abstain from sex. 

Now for some good news. Culex pipens and Aedes triseriatus are not vectors for Zika virus. This is great news because C. pipens is a widespread mosquito and is a vector for West Nile virus. If C. pipens were a vector, then Zika could spread throughout much of the world. However, there is still some bad news. Zika virus was recently found to not only replicate in C. quinquefasciatus, but it was also found in the salivary glands where it also replicated. To be vectored by an arthropod, a virus would need to pass through the gut barrier and then migrate to the salivary glands. Replication in the salivary glands is a good indicator that the arthropod might be a vector. This is a good review on arthropod transmission of plant viruses (the principles are the same for other arboviruses). If C. quinquefasciatus is a vector for Zika, then it could spread further than we are anticipating now. Vector transmission assays still need to be conducted to determine if it is a vector or not. 

The most interesting new study on Zika is the case controlled study that confirms that Zika causes birth defects. The results showed a strong correlation between detection of Zika virus in the mother and microcephaly in the baby. Further work is required to determine the exact risk associated with Zika infection during pregnancy, but at this point the role of Zika in causing birth defects is definitive. The authors did recommend that the TORCH acronym be changed to TORCHZ. I made an infographic awhile ago on whether Zika should be added to the list or not. I'll have to update it now.

My infographic on adding Zika to the list of TORCH pathogens. 

Friday, September 16, 2016

Hepatitis A virus: A new model system allows for basic research on the pathogenesis

Transmission electron micrograph of Hepatitis A virus. Credit: CDC/Betty Partin

New research helps to shed light on how Hepatitis A virus damages the liver cells. Using a mouse model system (which is a feat in of itself as this virus was previously found to only infect primates), the researchers were able to identify the mechanism that causes the damage. The virus induces the apoptosis pathway in the liver cells (this is often referred to as programmed cell death) as a result on an innate immune system response to infection. Apoptosis is a complex signaling pathway that is a safety system to limit the spread of infections and prevent unregulated cell growth (cancer). Wikipedia has a detailed article on apoptosis. 

An overview of signal transduction pathways for apoptosis. Credit: Wikipedia

Using the newly developed mouse model, researchers have already begun to unlock of of the mysteries of Hepatitis A virus with many more to come. But more importantly, the researchers were able to identify why mice are not a normal host for the virus (their interferon response overcomes the ability of the virus to infect them). Hopefully, this work will lead to new therapies to combat this important human pathogen.

Thursday, September 8, 2016

A gene from an edible fern is highly effective as an insecticide against whiteflies

Bemisia tabaci (also known as the silverleaf whitefly) feeding on a leaf. Via Wikipedia.

When I got home from work last night, I spent a few minutes on Facebook while waiting for dinner to cook and I stumbled on something that floored me on the page We Love GMOs and Vaccines. Researchers in India have developed the first GE crop to produce compounds to kill whiteflies. They began this project in 2007 and developed the first GE cotton plant by 2012; the paper was just accepted a couple of days ago. In their work, the researchers purified a compound, called Tma12, from an edible fern, Tectaria macrodonta, and then fed it to whiteflies. The researchers observed that a very small amount of the purified compound (1.49 μg/ml) was lethal to the whiteflies. From there, the gene for this compound was identified, cloned and later transformed into cotton.

Tectaria macrodonta via Flickr

From there, the researchers tested the GE-Tma12 cotton in field trials and found that plants expressing ~0.01% Tma12 in leaf material were resistant to whitefly feeding. Furthermore, the whiteflies didn't transmit virus to the plants before they died (more on that in a second). To test the safety of this GE plant, the researchers fed leaf material to rats and no histological or biochemical differences were observed between those fed the GE plant and those fed the control. Since Tma12 lacked any known allergen motifs and did not harm the rats, the researchers concluded that this GE trait would pose little risk to the public. 

It's quite a breakthrough for a group to develop a GE trait specific to whiteflies; however, that isn't what stunned me. It's the implication that this trait might have for my own work. Whiteflies are one of many arthropods that vector plant viruses. However, they transmit many plant viruses that are of great economic importance and can cause famines as they infect many staple crops that people grow in developing nations. Cassava gets cassava mosaic caused by several begomoviruses transmitted by whiteflies. Sweet potato gets viruses from three different genera (Begomovirus, Crinivirus and Ipomovirus). Cotton has a number of begomoviruses that infect it as does tomato, which also gets criniviruses. These are just a few examples of the many crops infected by whitefly-transmitted viruses. In fact, there are over a hundred different viral species transmitted by whiteflies. Some viruses, like ipomoviruses, are transmitted shortly after feeding whereas others, like the begomoviruses, are only transmitted after the whitefly has feed for a long time. The Tma12 trait would be most effective at preventing transmission of the viruses that take longer periods of feeding before transmission takes place. For the viruses that take only a few seconds of feeding, this would not control them.

The thing that struck me most is the way that whiteflies feed. They feed by piercing the leaf and sucking sap from the phloem tissue (think of this as the artery of the plant). There are many other insects that feed this way (many in the order Hemiptera), including many plant disease vectors from aphids to mealybugs to plant/leaf-hoppers to psyllids (a psyllid is responsible for transmitting the bacteria that causes citrus greening). It would be interesting to see if Tma12 is effective against other insects, especially these very important plant disease vectors.

But what does this all mean? As is, this new trait will help make cotton production more sustainable. If this trait were deployed in other crops, the impact of whitefly-transmitted plant viruses in food production could be greatly reduced. If it's effective against other vectors, then this could truly revolutionize agriculture and pest management. 

Wednesday, September 7, 2016

How effective is the chickenpox vaccine? In a word, very

A transmission electron microscopy image of Human herpes virus 3 (also known as the Varicella zoster virus), the virus that causes chickenpox and shingles. Via wikipedia

I've posted many times about the chickenpox and shingles on my page. It's a viral disease that many people catch as children, but the older you get, the worse the symptoms are with an increased risk of death. It also has the nasty habit of hiding out in people's nerves and reemerging later in life as a very painful condition called shingles. I've made three infographics on this virus and the vaccine that can prevent it, but there is new data on how effective the vaccine really is.

First the infographics:
An infographic on chickenpox.

An infographic on shingles.

An infographic on the impacts of the chickenpox vaccine.

The CDC has released new calculations on how effective this vaccine is with the two-dose series. The initial one-dose series reduced incidence of chickenpox by 90%. However, there were still outbreaks of the disease so researchers and healthcare professionals recommended a second dose. This second dose has been highly effective, reducing incidence a further 84.6% with the greatest impact on those 5 to 9 years old (89.3% reduction). Overall, the vaccine has reduced incidence by 97%. In some states, it was difficult to determine the incidence as the disease had been significantly reduced. 

There are some countries that don't use this vaccine (the UK being one); however, based on how effective this vaccine is, they have begun clinical trials of the vaccine. Hopefully, they adopt this vaccine; as it protects against both the chickenpox and later on shingles (if you are immune to the chickenpox without being infected by the virus, you don't get shingles). 

Tuesday, September 6, 2016

How viruses made us what we are- Muscle cells

Cross section of mouse muscle (in blue: labeling of nuclei; in green: labeling of muscle fiber membranes). Normal male mice display larger muscle fibers than those seen in mutant, syncytin knock-out mice.
Credit: François Redelsperger via ScienceDaily

I've previously talked on my page about how an ancient retrovirus that integrated into early mammals helped to drive our evolution in a number of ways, including being responsible for placenta formation. A retroviral envelope gene called syncytin helps the placenta form as it mediates cell-cell fusion. Previously researchers had observed an increased expression of this gene at the interface between the fetus and the mother which later gives rise to the placenta. 

New research expands what we know on the topic and suggests that these integrated syncythins are responsible for the increased muscle mass that males have. When this gene was knocked out in mice, the muscle cells were smaller (see the picture above) and the mice had a 20% reduction of muscle mass. However, this reduction in muscle mass was only observed in males. The researchers then confirmed that knocking out this gene resulted in smaller muscle cells by knocking syncytin out in sheep, dog and human primary myoblasts. The cell sizes were reduced 20-40% when synctin was silenced. These results not only demonstrate that syncytin is involved in muscle cell fusion, but that it is required for the increased muscle mass seen in male mammals. This could help explain some of the sexual dimorphism seen between male and female mammals.

This work adds to what we know about ourselves and how viruses have played a role in making us what we are.