A Tale of Two Flaviviruses

Virology in 2016 and 2017 saw a great deal of attention paid towards Zika Virus (ZIKV) outbreaks in the Americas. In addition, recent introduction of West Nile virus to the Americas as of 1999 sees the field of virology and infectious disease adapting to the potential for these infections in a wide variety of patient populations. Work very recently published by Robinson, Enriquez, and Ho synthesized a body of work surrounding the development of WNV and ZIKV in the Americas, specifically as infection and standards of treatment apply to Solid Organ Transplantation (SOT) patient populations. Given the knowledge that WNV and ZIKV are both flaviviruses, the analysis of incidence and epidemiology involved in flavivirus infection in SOT patients is essential to the development of therapeutic techniques for these types of infections. This review is novel in that it holistically reviews cases of flavivirus infection in SOT, where donor-derived disease and increased disease severity are continuing to be fully understood in immunocompromised patient populations. In analyzing these two sources of disease within the same context as a viral family, insight was gained as to the progress that has been made in the field regarding SOT infectious disease as a whole and suggests potential next steps for development of diagnostics and treatments for flaviviruses. As clinical and scientific understanding of this virus develops, it is essential for practicing physicians to continue to develop protocols to protect SOT and immunocompromised patients, in addition to driving research into the afflictions that do not have optimal treatments. Work continues to try and develop vaccines and treatments for the diseases caused by these flaviviruses, and has resulted in many new types of Immunoglobulin based assays for the detection of viral titers in patients. This work is especially important for the immunocompromised patient and SOT communities, as limited data suggests that both WNV and ZIKV infections become exaggerated and more dangerous for these populations. Future work also continues to focus on the treatment of mosquito vectors to prevent their spread of the disease, with researchers finding new ways to either combat the disease within the mosquito or to combat the mosquito itself, much like the work of those combatting Yellow Fever in the late 1800's.

Source: Robinson ML, Enriquez K, Ho DY. A Tale of Two Flaviviruses: West Nile Virus and Zika Virus in Solid Organ Transplantation. OBM Transplantation 2019;3(1):32; doi:10.21926/obm.transplant.1901038.

~Kyle Enriquez

Investigators Uncover a New Approach to Target Herpesviruses

Herpesviridae is a family of viruses that includes the infamous herpes simplex 1, herpes simplex 2, mononucleosis, and chickenpox/shingles. Lesser known is cytomegalovirus (CMV), a virus that infects over 50% of adults over the age of 40 and sometimes causes reinfection via different strains. The oblivion to infection is likely due to CMV’s lack of symptoms, at least in healthy individuals, that is. Infants and those with compromised immune systems can suffer birth defects or transplant failures as a result of CMV.

Recently, the Proceedings of the National Academy of Sciences of the United States of America (PNAS) published a paper which details CMV’s replication mechanism. Scientists previously knew that in addition to bringing its own genetic material into the cell, CMV also brought a tegument protein which allows for sustained lytic expression called PP71. However, because PP71 has a lifespan of a couple hours, they’d been confused about how replication is carried out in such a short period of time. This is where a newly discovered protein, IE1, comes in. Positive feedback of IE1 further sustains lytic expression, ‘taking over’ for PP71. To test this, different levels of IE1 operating under designated breakdown times were applied to synthetic CMV: normal degradation causes normal, efficient replication, but, as expected, faster degradation causes poor replication. These findings might relevant to the mechanisms of other more severe herpes viruses that are more exigent of a cure.

Read the full article here: https://www.contagionlive.com/news/investigators-uncover-a-new-approach-to-target-herpesviruses

-Isabella Duan

VITN Blog Post #3: Zika as a Potential Treatment for Glioblastomas

Glioblastomas, a malignant tumor affecting the brain or spine, are currently incurable. Many die each year from the fatal brain cancer. The recurrence is high, meaning that the cancer has a high tendency to return even after surgery, radiation and chemotherapy. Currently, researchers are naming glioblastoma stem cells (GSCs) as the culprit for this recurrence. However, a team of international researchers has made an interesting hypothesis: zika could target these GSCs.

The outbreak of Zika led to the important discovery of microcephaly in newborns. This is because the virus neural progenitor cells in the fetus of infected mothers. The hope was to have the zika virus specifically target the GSCs because they have similar properties to the cells that the zika virus attacks naturally. A study done on mice models showed that the virus could kill GSCs without posing much harm to differentiated normal brain cells.

Then, the team went on to determine if there was a way for the zika virus to be used without damaging the human body. A live attenuated zika vaccine called ZIKV-LAV was created by researchers at the University of Texas Medical Branch and has shown to fight infection while being harmless to its host. To see if the vaccine could work against GSCs, they inserted both GSCs from humans and the virus into mouse models. Mice that only got the virus developed tumors, while the onset of tumor development in mice that got GSCs and the virus was significantly delayed. This shows promise in the field of oncology. Hopefully, with further research, we could take something that’s bad and turn it into something life-saving.

Read more here:

https://www.sciencedaily.com/releases/2018/09/180918082105.htm

• Noah Magbual

VITN Blog #3: ELISA and RT-qPCR as diagnostic tools for Zika

The Zika epidemic that spread like wildfire in Central and South America produced extraordinary levels of panic among local populations and anxiety in nearby countries such as the United States. Some athletes even withdrew from the 2016 Olympic Games held in Rio de Janeiro for fear of contracting the virus. Zika infection does not generally leave long-lasting effects in either men or women not trying to conceive, but the most devastating images to emerge from the epidemic were of infants born to Zika-infected mothers. Many suffer from microcephaly, i.e. small head size due to abnormal brain development. These children often experience severe developmental delays, but one symptom not as acknowledged in the popular media is epilepsy, a seizure disorder.

This study examined the prevalence and severity of epilepsy in a cohort of infants with congenital Zika infection. About two thirds of infants did have some type of epilepsy, and the authors went on to characterize the seizure type, use of antiepileptic drugs, and electroencephalographic features. One notable characteristic was that the infants’ epilepsy was usually early-onset and drug-resistant, indicating a systemic and persistent disruption of normal brain function due to viral action on the growing fetus. However, I was most interested in the two techniques the authors used to diagnose Zika infection in the serum and cerebrospinal fluid samples obtained from the infants and their mothers: enzyme-linked immunosorbent assay (ELISA) for IgM antibody capture and quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) assay for detecting Zika’s genome.

In class, we discussed the distinction between IgM, IgG, and IgA antibodies. IgM are found as a result of recent infection, IgG as a result of previous exposure to disease or vaccination, and IgA in bodily secretions (live, attenuated vaccine produces IgA while inactivated vaccine does not). Dr. Ben Pinsky had briefly summarized the mechanism of ELISA: place antigen on a solid support, add the patient serum, add an antibody conjugated to an enzyme, add the substrate of that enzyme, and measure the resulting color change. ELISA is a common protocol in serology, which seeks to identify antibodies in the blood serum. Dr. Pinsky mentioned several problems with this approach, including cross-reactivity between antibodies to related viruses (e.g. Zika and another member of the Flaviviridae family) and the persistence of IgM antibodies past the acute period of infection. Therefore, IgM antibody capture cannot be used on its own for diagnosis of Zika.

We are all familiar with the basic biochemical principles underlying PCR, which uses DNA as its starting material. RT-qPCR exploits these same rules, but with RNA instead. Under the Baltimore classification, Zika virus is in Group IV: it has positive-sense single-stranded RNA. As a result, PCR cannot be used for amplification of Zika’s genetic material, creating a need for RT-qPCR. Since RT-qPCR is dependent on nucleic acids, it is more specific than serology (according to Dr. Pinsky, such molecular diagnostic tools are steadily replacing older, more conventional ones like ELISA). RT-qPCR first uses reverse transcriptase to generate complementary DNA (cDNA) from the viral RNA template. That cDNA can then undergo PCR for amplification and further analysis such as sequencing for identification of Zika. Interestingly, RT-qPCR can be performed in just one step (in which reverse transcription and PCR occur in a single tube) or two, in which the reactions are separate. The number of hours that RT-qPCR takes varies depending on the chosen assay, but its analytical sensitivity makes it extraordinarily valuable for diagnosis.

The use of these two diagnostic techniques in this study demonstrates how important technological advances are to scientific investigation, especially in the field of infectious disease.

Study: “Epilepsy Profile in Infants with Congenital Zika Virus Infection” (https://www.nejm.org/doi/full/10.1056/NEJMc1716070)

- Panos Vandris

Herpes Virus and Nano-particles: The Perfect Storm

Approximately 80% of the human adult population has been infected

or will be infected with some strain of herpes virus. Although most of
these cases are asymptomatic or only mildly symptomatic, the disease
can actually be lethal for a small portion of the population such as those
with compromised immune systems like babies or people with advanced
HIV infection. However a recent paper that was published within the
scientific community brings to light a new concern when it comes to herpes
virus.

Persistent herpes virus infection is caused by an infection that becomes
latent in a person, usually thanks to immune system response to keep the
virus at bay. Typically this isn’t of much concern, however, when this is combined
with the inhalation of environmental nano-particles, the infection can become
reactivated leading to an acute infection which can cause severe tissue damage
or result in chronic lung disease such as idiopathic pulmonary fibrosis.

What are these nano-particles that the researchers talk about? They are
combustion derived nano-particles that you can find in diesel exhaust, diesel soot,
or welding fumes as a few examples. There is also a growing concern about
nanotechnology and how nano-particles produced from nanotechnology could affect
human health as it becomes more prevalent.

According to the research, several exposures of latent virions in the lung to
nano-particles restores a molecular signature characteristic for acute viral infection.
In other words, these nano-particles are inducing viral replication. Researchers still
don’t know what the exact mechanisms for this are, but they are working to decipher
it and hopefully develop preventive measures against a possible surge of complicated
herpes virus infections we could be seeing in the future.

-Renata Starbird

http://blogs.biomedcentral.com/on-health/2018/09/18/exposure-nanoparticles-can-activate-herpesvirus-viruses-lungs-winner-particle-fibre-toxicology-best-paper-award-2018/

VITN Blog Post #3: Vampire Facial May Expose Clients to HIV

Health officials in New Mexico have advised clients of a 'vampire facial' to get HIV, HBV, and HCV testing after unsafe practices were revealed at a spa in Albuquerque. A vampire facial involves drawing a person's blood, placing it into a centrifuge and extracting the plasma, and injecting the plasma into the face with a micro-needling pen. The plasma contains nutrients, proteins, and growth factors that stimulate the skin and provides extra collagen. When the equipment lacks proper sterilization, patients can be exposed to various blood-borne diseases. Consumers can be more cautious by monitoring the sterilization/disposal methods used by doctors for micro-needles and ensuring that their spa is 'vampire certified.' Proper sanitation and disposal methods can help prevent blood-borne viruses from spreading from one patient to the other.
Avery Muniz
Viruses in the News 2018
Link: https://www.cnn.com/2018/09/13/health/vampire-facial-new-mexico-hiv-test-bn/index.html 

VITN Blog Post #2: Cucumber Mosaic Virus

Almost every virus we have spoken about in Viruses in the News has been endemic to humans, animals, or bacteria. But what about plants? In a recent news report by HortiDaily, Arian Shala describes a recent epidemic in the Balkan area. The problem: cucumber mosaic virus and tomato spotted wilt virus.

Cucumber mosaic virus and tomato spotted wilt virus has caused immense destruction. Croatia has around 500 acres dedicated to greenhouse pepper farming. And with cucumber mosaic virus, many farmers were harvesting 40 to 80% less than they usually do for pepper. Such destruction has decreased supply for pepper, raising the price by nearly 1 euro. Tomato plants have also been affected by this epidemic.

Symptoms of cucumber mosaic virus and tomato spotted wilt virus include stunted growth and reddish-brown stripes. And the organism that seems to transfer the disease are aphids.

Researchers are currently working towards selectively growing plants that are resistant to cucumber mosaic virus and tomato spotted wilt virus.

See article here for more information: http://www.hortidaily.com/article/45719/Pepper-virus-wreaks-havoc-in-Balkan-horticulture

-Kyle Feliciano