Challenges posed by equine flu virus explored in fresh review

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The structure of the equine influenza virus. EIV is a segmented RNA virus possessing eight (single) segmented negative sense RNA strands. Segmented genome encodes eight structural proteins and at least two non-structural proteins. Image: Singh et al. https://doi.org/10.3389/fmicb.2018.01941
The structure of the equine influenza virus. EIV is a segmented RNA virus possessing eight (single) segmented negative sense RNA strands. Segmented genome encodes eight structural proteins and at least two non-structural proteins. Image: Singh et al. https://doi.org/10.3389/fmicb.2018.01941

Better methods for assessing vaccine potency need to be designed to improve the protection of horses from equine influenza, a review suggests.

Equine influenza is a highly contagious respiratory disease of horses mainly caused by the H3N8 strain. It is a major problem globally.

There are many equine influenza virus subtypes circulating, vaccines for which provide no cross-protection to other strains.

Hippocrates described a disease resembling equine influenza as far back as 412 BC.

The virus transmits easily by direct contact and inhalation, which has made its spread global, leaving few areas untouched.

Raj Singh and his colleagues, in a comprehensive review of the virus published this week in the journal Frontiers in Microbiology, say it is continuously evolving, with changes at the amino acid level making the control program a “‘tedious task”.

Transmission of EIV. Droplet infection is an important mode of transmission. Transmission between animals includes crowded housing practices, non-vaccination, young horses of 1–5 years and international trade. Dog gets EIV by consuming infected dead horse meat. Image: Singh et al. https://doi.org/10.3389/fmicb.2018.01941
Transmission of EIV. Droplet infection is an important mode of transmission. Transmission between animals includes crowded housing practices, non-vaccination, young horses of 1–5 years and international trade. Dog gets EIV by consuming infected dead horse meat. Image: Singh et al. https://doi.org/10.3389/fmicb.2018.01941

Recent advances in diagnostics have led to efficient surveillance and rapid detection of equine flu infections at the onset of outbreaks, they noted.

“Recurrent vaccination failures against this virus due to antigenic drift and shift have been disappointing,” they said. “However, better understanding of the virus pathogenesis would make it easier to design effective vaccines.”

A better understanding of its genetics and molecular biology would help in estimating the rate of evolution and occurrence of pandemics in future, they said.

The 13-strong review team noted that equine flu outbreaks have regularly been witnessed in non-vaccinated as well as vaccinated herds.

Continuous emergence of newer strains due to mutations is yet another hindrance to finding a definitive solution through vaccination.

Vaccination against the virus has been employed since the 1960s.

“However, its efficacy is still a matter of debate due to the use of less potent vaccines, improper vaccination schedule and also use of outdated virus strains,” they noted, as well as continuing drift in the viral genome.

Replication and pathogenesis of EIV. EIV damages the upper and lower respiratory tract's ciliated epithelial cells thereby causes inability to clear foreign substances. Spike glycoprotein HA fastens to the receptors present on the respiratory epithelial cells and it enters the cells by endocytosis. After endocytosis, EIV undergoes fusion and uncoating. Opening of M2 channel leads to proton entry and subsequent release of viral RNA followed by synthesis of viral structures leading to assembly of EIV. EIV is released from the infected cells by the process of budding. Image: Singh et al. https://doi.org/10.3389/fmicb.2018.01941
Replication and pathogenesis of EIV. EIV damages the upper and lower respiratory tract’s ciliated epithelial cells thereby causes inability to clear foreign substances. Spike glycoprotein HA fastens to the receptors present on the respiratory epithelial cells and it enters the cells by endocytosis. After endocytosis, EIV undergoes fusion and uncoating. Opening of M2 channel leads to proton entry and subsequent release of viral RNA followed by synthesis of viral structures leading to assembly of EIV. EIV is released from the infected cells by the process of budding. Image: Singh et al. https://doi.org/10.3389/fmicb.2018.01941

Although no human cases in practice have been reported, a human pandemic in 1889 was attributed to the H3N8 equine influenza virus. Other influenza-like disease epizootics have been observed, but, as with the 1889 outbreak, they occurred before the advent of various serological and molecular tests to detect the virus.

The authors described evidence of human infection as sparse, but did note that the virus had been shown in an experimental setting to induce the production of antibodies.

In other species, the evidence is much clearer. Reports confirm that the equine flu virus can affect dogs, cats and camels.

“This should raise alarm,” they wrote, “as dogs are closely associated with humans and they may act as a mixing vessel for equine and human influenza virus facilitating emergence of new human influenza strains.

“It is imperative now to develop an efficient canine influenza virus vaccine and imply proper vaccination strategy in dogs to prevent such infections.”

The authors concluded that recent advances in diagnosis and surveillance of the virus need to be exploited to their full potential to monitor the epidemiology of this virus in details and record cases of equine flu.

Different vaccine platforms available for EIV. Platforms include killed vaccine, inactivated vaccine, subunit vaccine, DNA vaccine, subunit vaccine, vectored vaccine, reverse genetics-based vaccine. Image: Singh et al. https://doi.org/10.3389/fmicb.2018.01941
Different vaccine platforms available for EIV. Platforms include killed vaccine, inactivated vaccine, subunit vaccine, DNA vaccine, subunit vaccine, vectored vaccine, reverse genetics-based vaccine. Image: Singh et al. https://doi.org/10.3389/fmicb.2018.01941

Regular monitoring of horses for equine flu strains is necessary to enable effective vaccination strategies to be employed.

“Better methods for assessing vaccine potency also need to be designed. Regular monitoring and surveillance of the virus can also help to update the available vaccine with the new variants that occur.”

Now is the right time to embrance various advancements in vaccine manufacture to develop safe and effective vaccines against the virus, they said.

“Also, vaccine delivery methods can be standardized for superior quality of immune response.”

The full review team, from a range of institutions in India, Britain and Switzerland, comprised Raj K. Singh, Kuldeep Dhama, Kumaragurubaran Karthik, Rekha Khandia, Ashok Munjal, Sandip K. Khurana, Sandip Chakraborty, Yashpal S. Malik, Nitin Virmani, Rajendra Singh, Bhupendra N. Tripathi, Muhammad Munir and Johannes H. van der Kolk.

Singh RK, Dhama K, Karthik K, Khandia R, Munjal A, Khurana SK, Chakraborty S, Malik YS, Virmani N, Singh R, Tripathi BN, Munir M and van der Kolk JH (2018) A Comprehensive Review on Equine Influenza Virus: Etiology, Epidemiology, Pathobiology, Advances in Developing Diagnostics, Vaccines, and Control Strategies. Front. Microbiol. 9:1941. doi: 10.3389/fmicb.2018.01941

The review, published under a Creative Commons License, can be read here

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