Free-virus and cell-to-cell transmission in models of equine infectious anemia virus infection.

This research investigates the transmission methods of the Equine Infectious Anemia Virus (EIAV) and how two different strains of the virus can impact the course of the disease. This was done by formulating a set of equations to estimate and demonstrate the virus-cell dynamics. Furthermore, two endemic equilibria were revealed – a coexistence equilibrium and a resistant strain equilibrium.

Transmission of EIAV

• Equine Infectious Anemia Virus (EIAV) is a lentivirus in the retrovirus family that primarily affects horses and ponies.
• Two specific strains were examined – one being the sensitive strain, which potentially can be neutralized by antibodies, and the resistant strain that appears to be immune to antibody neutralization.
• EIAV can be transmitted to healthy cells through ‘free virus’ – or using molecules external to the cell – or alternatively, a direct cell-to-cell transfer.
• It was hold uncertain what the proportion of transmission was from free-virus or from cell-to-cell, which was one of the primary motivations for the study.

Investigating Virus-Cell Dynamics

• The researchers formulated a system of ordinary differential equations (ODEs) to estimate and demonstrate how the virus interacts with the cellular structures it infects.
• They also took into account two different types of models, one of which being a Markov chain model, while the other was a branching process approximation near the infection-free equilibrium (IFE).
• The basic reproduction number — noted as R0 — is defined as the maximum of two reproduction numbers, R0s and R0r, which correspond to the sensitive strain and the resistant strain respectively.
• If R0 is greater than one, the infection is likely to persist with at least one of the two strains. However, for small infectious doses, neither strain may persist in the Markov chain model.

Endemic Equilibria

• The IFE is shown to be globally asymptotically stable when the basic reproduction number is less than one. This infers that the infection tends to stabilize over time in an infection-free equilibrium if the basic reproduction number is less than one.
• If not, two endemic equilibria tend to exist. These include a coexistence equilibrium – where both strains coexist – and a resistant strain equilibrium – where resistance dominates, reflecting the survival of the strongest.

General Observations and Model Illustrations

• Practical examples were also given, using parameter values that would apply to EIAV to illustrate the dynamics of both models.
• The results highlighted the importance of the proportion of cell-to-cell and free-virus transmission since it seems to impact the progression of the infection – whether it leads to infection clearance or persistence in either coexistence of both strains or to dominance by the resistant strain.