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Matonaviruses and Togaviruses are extremely small—about 70 nanometres across, compared with a human hair being around 70,000 to 10,000 nanometres thick. They are encased in a protein shell and appear as tiny spheres covered by a lipid membrane.  Embedded on the surface of the membrane are multiple minuscule spikes of about six nanometres in length. 

Matonaviruses and Togaviruses enter and infect human cells by attaching to specific receptors on a cell’s surface. Chikungunya, Ross River, Mayaro and O’nyong nyong viruses—which are all from the Alphavirus side of the Togavirus family—invade host cells by fusing with a protein known as Mxra8, which is found on a range of human cell types, including skin cells and immune cells.

The Rubella virus infects human cells by binding to different receptors, including one known as myelin oligodendrocyte glycoprotein, or MOG.  

Scientists are still working on identifying exactly how EEEV, WEEV and VEEV attach to and infect human cells. In a recent investigation conducted using new gene-editing technology known as CRISPR-Cas9, researchers found that a receptor on human cells used by another Togavirus, Semliki Forest Virus, is also compatible with two other viruses in the Togavirus family, EEEV and Sindbis virus. 

Chikungunya

Chikungunya virus was first identified in Tanzania in the 1950s. Since then the disease has caused infections and deaths in many countries in Africa and Asia. Most recently it has extended its infectious reach into Europe and the Americas as climate change has opened up new habitats for its main carriers – Aedes mosquitos – to thrive.

In 2004, the Chikungunya virus emerged in Kenya and spread in an explosive outbreak, causing a human disease epidemic across several countries in and around the Indian Ocean, including the Seychelles, Mauritius, Madagascar and eventually also India. Many millions of people were infected during the 2004 to 2007 outbreak, and because health systems in many of the affected countries were weak, the Chikungunya outbreak put enormous strain on them. Imported cases from this epidemic—the largest Chikungunya outbreak so far recorded—were subsequently detected in other parts of Asia as well as in Australia, the United States, Canada and Europe.  

In 2007, an outbreak of Chikungunya virus infections emerged for the first time in Europe, in Italy. Then France reported cases of the disease in 2010 and 2014. And in late 2013, Chikungunya emerged in the Caribbean and quickly spread in the Americas, leading to more than more than 1.2 million cases being reported to Pan American Health Organization in the Americas during 2013 and 2014. This year, 2023, a large and deadly outbreak of Chikungunya has erupted in Paraguay, Brazil, Argentina and Bolivia, so far infecting more than 300,000 people and killing 300 of them. 

Eastern Equine Encephalitis Virus

Eastern Equine Encephalitis Virus is rare in people but highly pathogenic, getting into the brain and causing severe encephalitic disease. One of the most severe human outbreaks in the United States of EEEV was during 2019. Among 38 confirmed cases, 15 were deadly – giving a case fatality rate of almost 40 percent. 

Rubella

Rubella was endemic worldwide before an effective vaccine was developed in the mid-1960s and deployed widely beginning in the early 1970s. Before this widespread immunisation, there were regular epidemics of Rubella virus every six to nine years, with the most vulnerable age group being children from four to nine years old.

Among the most notorious Rubella outbreaks in the United States was from 1964 to 1965, when an epidemic of the virus infected 12.5 million Americans, an estimated one in 15 of the U.S. population. The epidemic led to more than 11,000 stillbirths, miscarriages and abortions among women had been infected while pregnant and the 20,000 or more babies born with congenital abnormalities in the wake of the outbreak became known as “Rubella babies”. 

Fortunately, disease detectives have made great progress in their search for ways to defend people against the prime suspect in the Matonavirus family.  In 1964, working in his Wistar Institute laboratory, the vaccinologist (and now a scientific advisor to ����VR��Ƶ) Stanley Plotkin invented the world’s first Rubella vaccine. The vaccine is now administered in many countries as a single shot in routine childhood immunisation programmes, or as part of the triple shot MMR (Measles, Mumps and Rubella) immunisation. While use of the vaccine has dramatically reduced Rubella infections worldwide, poverty, conflict and weak health systems in some countries mean it is still not being accessed by everyone. There are still more than 100,000 children born with Congenital Rubella Syndrome each year.  

Among the Alphavirus group within the Togavirus family, progress in the 75 years since Chikungunya disease was first discovered was initially slow but has picked up dramatically in recent years. Multiple lines of enquiry against Chikungunya and its relatives have been pursued by scientific researchers around the world, leading to a wide range of promising preclinical and clinical vaccine candidates being developed. Among those are three vaccine candidates being developed with support from ����VR��Ƶ and the European Commission, including a live-attenuated Chikungunya vaccine candidate from the French pharmaceutical company Valneva. The Valneva vaccine became the world's first licenced Chikungunya vaccine in November 2023, when it gained regulatory approval from the U.S. Food and Drug Administration. 

Also on the Alphavirus side of the Togavirus family, scientists are working to develop human vaccines against the three Equine Encephalitis viruses EEEV, VEEV and WEEV. One line of enquiry has involved taking antibodies from the blood of human survivors of EEEV to investigate which ones are able to neutralise EEEV infection and could therefore be used as a basis for a monoclonal antibody therapy or vaccine.