Virus World

Discover how Aedes aegypti mosquito eggs harboring ZIKV and CHIKV pose a new public health challenge, urging a revamp in control strategies. A groundbreaking discovery by scientists at the Federal University of Goiás (UFG) has unveiled that Aedes aegypti mosquito eggs can carry the ZIKV and CHIKV viruses, responsible for Zika and chikungunya respectively. This finding, highlighting a vertical transmission route, underscores a significant public health concern and calls for enhanced surveillance and control measures.

Unveiling the Mechanism of Vertical Transmission

The study, published in the source , marks a paradigm shift in understanding how these viruses are spread. Traditionally, transmission was thought to occur horizontally, with mosquitoes becoming vectors after biting an infected host. However, the detection of ZIKV and CHIKV in mosquito eggs before they hatch means mosquitoes can be born already infected, ready to spread the virus without prior contact with an infected host.

Implications for Public Health and Surveillance

Diego Michel Fernandes da Silva, the study's coordinator and a doctoral student at UFG, emphasized the significance of this discovery for public health. With mosquitoes capable of being born as carriers of these viruses, the potential for rapid spread increases, especially in urban environments. This adaptation mechanism allows for easier dispersal and poses a considerable challenge for controlling outbreaks of Zika and chikungunya. The study's findings necessitate a reconsideration of current prevention strategies, urging health authorities to intensify local epidemiological surveillance and explore innovative ways to eliminate the mosquito population.

Research Methodology and Findings

The research team captured Aedes aegypti eggs and adult mosquitoes across three major regions of Goiânia, Goiás, from January to September 2022. After isolating the heads and thoraxes of 1,570 adult females for analysis, the eggs were raised in laboratory conditions until they hatched. Among these, two groups tested positive for CHIKV and one for ZIKV, confirming that vertical transmission had occurred and that these mosquitoes could transmit the viruses upon reaching maturity. This revelation has profound implications for the fight against diseases like Zika and chikungunya. By demonstrating that viruses can be transmitted vertically from mosquitoes to their offspring, the study not only expands our understanding of these diseases' epidemiology but also underscores the urgent need for innovative control measures. As we grapple with the potential for increased transmission, this research serves as a critical call to action for health authorities worldwide to reassess and fortify their disease prevention strategies.

Cites Study Published in Revista da Sociedade Brasileira de Medicina Tropical (2024):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10890825/ 

The spread of vector-borne viruses, such as CHIKV, is a significant public health concern in the Americas, with over 120,000 cases and 51 deaths in 2023, of which 46 occurred in Paraguay. Using a suite of genomic, phylodynamic, and epidemiological techniques, we characterized the ongoing large CHIKV epidemic in Paraguay.

Preprint in medRxiv (April 17, 2023):

https://doi.org/10.1101/2023.04.16.23288635 

A combination of the Zika virus and Chikungunya, two mosquito-borne infections, increase stroke risk, a new study reports. University of Liverpool researchers and Brazilian collaborators have been investigating the link between neurological disease and infection with the viruses Zika and chikungunya. These viruses, which mostly circulate in the tropics, cause large outbreaks of rash and fever in places like Brazil and India. Zika is widely known to cause brain damage in babies following infection in pregnancy, but the new research shows it can also cause nervous system disease in adults. The study of 201 adults with new onset neurological disease, treated in Brazil during the 2015Zika and 2016 chikungunya epidemics, is the largest of its kind to describe the neurological features of infection for several arboviruses circulating at the same time. The new research shows that each virus can cause a range of neurological problems. Zika was especially likely to cause Guillain-Barre syndrome, in which the nerves in the arms and legs are damaged. Chikungunya was more likely to cause inflammation and swelling in the brain (encephalitis) and spinal cord (myelitis). However, stroke, which could be caused by either virus alone, was more likely to occur in patients infected with the two viruses together.

Stroke occurs when one of the arteries supplying blood to the brain becomes blocked. The risk of stroke is known to be increased after some types of viral infection, like varicella zoster virus, which causes chickenpox and shingles, and HIV. Stroke is also being recognised increasingly as a complication of COVID-19. This has important implications for the investigation and management of patients with viral infection, as well as for understanding the mechanisms of disease. In total 1410 patients were screened and 201 recruited over a two-year period at Hospital da Restauração in Recife, Brazil. Comprehensive PCR and antibody testing for viruses was carried out in Fiocruz laboratories. Of the 201 patients admitted with suspected neurological disease linked to Zika, chikungunya or both, 148 had confirmation of infection on laboratory testing, around a third of whom had infection with more than one virus. The median age of patients was 48, and just over half the patients were female. Only around 10% patients had fully recovered at discharge, with many having ongoing issues like weakness, seizures, and problems in brain function. Of the stroke patients, who were aged 67 on average, around two thirds had infection with more than one virus.

Many of the people who had a stroke had other stroke risk factors, such as high blood pressure, indicating that stroke following Zika and chikungunya viral infection may most often be seen in those who are already high risk. Dr Maria Lúcia Brito Ferreira, neurologist and head of department at Hospital da Restauração, leading the Brazilian team said: “Zika infection most often causes a syndrome of rash and fever without many long-term consequences, but these neurological complications — although rare — can require intensive care support in hospital, often result in disability, and may cause death.” ..

Original Study Published in The Lancet Neurology (October 2020):

https://doi.org/10.1016/S1474-4422(20)30232-5

Originally from Africa, chikungunya is aptly named. It derives from a word in the Kimakonde language meaning "to become contorted," because the severe muscle and joint pains endured by the patients prevent them from moving normally or performing their daily activities.

While the clinical manifestations of the disease are well understood, the mechanisms by which the virus  infects human cells and multiplies remain poorly elucidated. Several studies have already identified certain host cell factors implicated in the replication of the virus. However, none has succeeded in explaining why the virus preferentially targets the muscle and joint cells, causing these clinical signs.

Researchers from Inserm, CNRS and Université de Paris led by Dr. Ali Amara at the AP-HP Saint-Louis Hospital Research Institute in Paris, in collaboration with Marc Lecuit's team from Institut Pasteur, Inserm and Université de Paris now report that the FHL1 protein is a key cellular factor for the replication and pathogenesis of chikungunya. FHL1 is a molecule present mainly in the muscle cells and fibroblasts, the preferred targets of the virus. Usually, FHL1 contributes to healthy muscle physiology and it is now thought to be diverted from that function by the virus to ensure its replication in the target cells.

To conduct this study, Amara's team used the CRISPR-Cas9 technology to screen the genome of human cells in order to identify the host factors necessary for viral replication. In doing so, it isolated the gene coding for the FHL1 protein. The team then conducted a series of experiments showing the incapacity of the virus to infect cells whose FHL1 expression had been abolished. In addition, the researchers have shown that the virus was incapable of multiplying within cells derived from patients suffering Emery-Dreifuss muscular dystrophy—a rare genetic disease. This muscle disease is the result of mutations of the FHL1 gene responsible for the breakdown of the FHL1 protein. The researchers have shown that the cells of these patients are resistant to the virus. Finally, the researchers performed in vivo experiments in mice whose Fhl1 gene was invalidated. They have shown that these animals are totally resistant to infection and do not develop the disease, whereas the virus multiplies and causes major muscle lesions in mice expressing a functional FHL1 protein. These observations demonstrate that the FHL1 protein plays a key role in chikungunya virus replication and pathogenesis.

The precise role played by FHL1 in the viral infection is not fully understood. The researchers have discovered that FHL1 interacts with a viral protein known as nsP3. It is when binding to this that FHL1 participates in the replication of the virus. "We now want to understand this interaction in molecular detail. The next step is to define why FHL1 is so specific to the chikungunya virus, and to decipher its mechanism of action at the molecular level. Elucidating the molecular structure of the FHL1-nsP3 complex could represent a major step forward in the development of antivirals that block the replication of the virus," say Ali Amara and Laurent Meertens, the Inserm researchers in charge of the study. At present, only symptomatic treatments are available for patients infected with chikungunya.

Study published in Nature on Sept. 25, 2019:

https://doi.org/10.1038/s41586-019-1578-4

The female mosquito needs your blood to grow her eggs. Please don’t feel singled out. She bites everyone. There is no truth to the myths that mosquitoes prefer women over men or blondes and redheads over those with darker hair. She does, however, play favorites. Type O blood seems to be the vintage of choice. Stinky feet emit a bacterium that woos famished females, as do perfumes. As a parting gift, she leaves behind an itchy bump (an allergic reaction to her saliva) and potentially something far worse: infection with one of several deadly diseases, including malaria, Zika, West Nile, dengue and yellow fever.

The mosquito-borne disease, which can be fatal to newborns, has killed at least 350 people this year. The FDA's approval is expected to speed up the vaccine's global rollout. This year, about 440,000 chikungunya cases, including 350 deaths, have been reported as of September. There is currently no specific drug to treat chikungunya. South America and South Asia have seen the most number of cases this year. The vaccine named Ixchiq has been approved for those aged 18 and above and are at high risk of contracting the disease, the FDA said on Friday. It was developed by Europe's Valneva and will be administered in a single shot. "Infection with chikungunya virus can lead to severe disease and prolonged health problems, particularly for older adults and individuals with underlying medical conditions," senior FDA official Peter Marks said.

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18–50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik.

The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose. Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that has caused outbreaks in various regions of the world. Here the authors present safety and immunogenicity data from a phase 1 trial with the simian adenovirus vectored vaccine ChAdOx1 Chik, showing induction of neutralizing antibodies to four CHIKV lineages.

Published in Nat. Communications (July 30, 2021):

https://doi.org/10.1038/s41467-021-24906-y

A new type of vaccine that can be stored at warmer temperatures, removing the need for refrigeration, has been developed for mosquito-borne virus Chikungunya in a major advance in vaccine technology. The findings, published in Science Advances today [Wednesday 25 September], reveal exceptionally promising results for the Chikungunya vaccine candidate, which has been engineered using a synthetic protein scaffold that could revolutionise the way vaccines are designed, produced and stored.

Researchers from the University of Bristol and the French National Centre for Scientific Research (CNRS) in Grenoble, France, teamed up with computer technology giant Oracle to find a way to make vaccines that are thermostable (able to withstand warm temperatures), can be designed quickly and are easily produced. “We were working with a protein that forms a multimeric particle resembling a virus but is completely safe, because it has no genetic material inside, said Pascal Fender, expert virologist at CNRS. “Completely by chance, we discovered that this particle was incredibly stable even after months, without refrigeration.”

“This particle has a very flexible, exposed surface that can be easily engineered, added Imre Berger, Director of the Max Planck-Bristol Centre for Minimal Biology in Bristol. “We figured that we could insert small, harmless bits of Chikungunya to generate a virus-like mimic we could potentially use as a vaccine.” To validate their design, the scientists employed cryo-electron microscopy, a powerful new technique recently installed in Bristol’s state-of-the-art microscopy facility headed by Christiane Schaffitzel, co-author of the study. Cryo-EM yields very large data sets from which the structure of a sample can be determined at near atomic resolution, requiring massive parallel computing.

Enabled by Oracle’s high-performance cloud infrastructure, the team developed a novel computational approach to create an accurate digital model of the synthetic vaccine. University of Bristol IT specialists Christopher Woods and Matt Williams, together with colleagues at Oracle, implemented software packages seamlessly on the cloud in this pioneering effort. Christopher explained: “We were able to process the large data sets obtained by the microscope on the cloud in a fraction of the time and at much lower cost than previously thought possible.” “Researchers have had a long tradition of building and installing their own super computers on-premises, but cloud computing is allowing them to run large data sets in record time, with fast connectivity and low latency. This is helping them crunch data and make scientific breakthroughs much faster. Going forward, technologies like machine learning and cloud computing will play a significant part in the scientific world, and we are delighted we could help the researchers with this important discovery,” added Phil Bates, leading cloud architect at Oracle.

The particles the scientists designed yielded exceptionally promising results in animal studies, soundly setting the stage for a future vaccine to combat Chikungunya disease....

Published on September 25, 2019 in Science Advances (Open Access):

https://doi.org/10.1126/sciadv.aaw2853

Researchers develop way to ID cells infected with chikungunya. Since chikungunya virus emerged in the Americas in 2013, it has infected millions of people, causing fever, headache, rash, and muscle and joint pain. For some people, painful, debilitating arthritis lasts long after the other symptoms. Now, researchers at Washington University School of Medicine in St. Louis have figured out a way to detect cells infected with chikungunya virus that survive the infection. They genetically modified the virus such that it activated a fluorescent tag within cells during infection. Months after the initial infection, the researchers could detect glowing red cells still harboring viral RNA. The study, in mice, opens up new ways to understand the cause of – and find therapies for – chronic viral arthritis. The findings are published August 29, 2019 in PLOS Pathogens.

Senior author Deborah Lenschow, MD, PhD, an associate professor of medicine and of pathology and immunology, and co-first author and graduate student Marissa Locke answered questions about the research, which was conducted in collaboration with co-first author Alissa Young, PhD, co-author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine, and others.

How common is chronic arthritis caused by chikungunya infection?

Lenschow: Between 30% and 60% of people infected with chikungunya virus go on to develop chronic arthritis that can last up to three or four years after infection. Researchers had found viral RNA in joint fluid from people with chronic arthritis, but they didn’t know whether the virus had gone dormant or whether it was still multiplying and infecting new cells at an undetectably low level.

Locke: Nobody had located the cells that harbored the viral RNA. This matters because if we can’t find the infected cells, we can’t study them.

Where did you find the virus, and what does that tell you about the cause of chronic arthritis?

Locke: We found the virus in muscle cells and in connective tissue cells in the skin and muscle. These cells likely had become infected within the first week of the virus invading the body, yet managed to survive. They were still there in the muscles and joints up to 114 days after infection, and they still had viral RNA inside them.....

Findings published  August 29 on PLOS Pathogens (Open Access):

https://doi.org/10.1371/journal.ppat.1007993

The French vaccine developer Valneva has received a €21M ($23.4M) grant to catch up with the competition in commercializing the first potential vaccine for the chikungunya virus. Coming from the nonprofit Coalition for Epidemic Preparedness Innovations (CEPI), the grant will boost the manufacturing and development of Valneva’s vaccine for the tropical disease chikungunya, which causes fever and can trigger chronic pain in the joints. Chikungunya has long been a problem in developing countries with endemic tropical diseases, but has received less attention from developed countries until recently. However, climate change could increase the range of disease-carrying mosquitoes, and chikungunga outbreaks in Europe could become more common. Companies developing vaccines for the disease could deliver an important weapon in the fight against the disease. 

In May, the vaccine showed the potential to protect against the virus in a phase I trial. As the company has already calculated an optimal dose, Valneva’s one-shot vaccine could skip phase II and head directly to phase III.

The Austrian biotech Themis Bioscience is also developing a vaccine for chikungunya, which is expected to enter phase III later this year. With a phase III trial expected to begin in early 2020, Valneva might narrow Themis’ lead in the race to get the first chikungunya vaccine to the market. 

The CEPI allocates grants to fund the development of vaccines against infections causing humanitarian crises. CEPI also recently provided a 19M euros grant to Themis, with the aim of accelerating vaccines for chikungunya and other diseases to the market.