Experimental Infection of Ponies with Equine Influenza A2 (H3N8) Virus Strains of Different Pathogenicity Elicits Varying Interferon and Interleukin-6 Responses

Abstract

The production of interferon (IFN), interleukin-6 (IL-6), and tumor necrosis factor (TNF) was monitored in horses during the course of influenza A2 virus infections. The effects of two virus strains, Newmarket/2/93 and Sussex/89, were compared, of which the latter is considered the more pathogenic in terms of clinical signs. Ten naive ponies were infected with influenza A/equine/Sussex/89 and 10 with influenza A/equine/Newmarket/2/93, respectively. As expected ponies infected with Sussex/89 showed the most pronounced clinical signs but there was no notable difference in viral excretion compared with Newmarket/2/93. IFN was detected in nasal secretions of all ponies infected with Sussex/89 but only in 2 ponies infected with Newmarktet/2/93. IFN was not detected in serum of any animal. IL-6 activity was detected in nasal secretions of all experimental animals from day 2 and onwards, but showed markedly higher IL-6 responses were observed in ponies infected with Sussex/89. No TNF activity was detected in any of the samples collected. In summary, equine influenza A 2 infections elicited local, and in some cases systemic, IFN and IL-6 responses in the ponies. Interestingly, there was some evidence that the duration and levels of cytokine responses may be related to the pathogenicity of the influenza strains.

Dynamics of Influenza Virus Infection and Pathology

“…Our calibrated model of viral and immune dynamics allows exploration of how variations in IFN induction and IFN efficiency (defined here as the rate at which IFN induces a refractory state in a susceptible target cell) can affect the spectrum of virus replication, tissue damage, and subsequent pathology. Experimental data show differences between engineered influenza virus mutants (37,44) and different virus strains (48) in how they interact with the innate immune system and cause disease; much of this variation is mediated by viral factors (including different forms of the NS1 protein [37,44]), which can affect either the induction of IFN or its efficiency in limiting virus growth (12,17).…”

“…With this dynamic range, the model can describe some observed phenomena. For example, Wattrang et al compared virus shedding and IFN levels in two groups of horses infected with different strains of equine influenza virus (48). While the titers of virus shed were similar, the total IFN produced was greater and the clinical signs were more severe following infection with one strain.…”

Factors Influencing Serum Amyloid Type A (Saa) Concentrations in Horses

“…Generically, vaccination causes a moderate increase of SAA, which begins at 24 hours, persists for 96 hours and decreases in 3 -4 days [62,63]. The A2 influenza virus produces a type of local response which in some cases is systemic and is due to the synthesis of IL-6 and TNF-α [64]. Similarly, inoculation of endotoxins produced by Escherichia coli induces a marked release of IL-1 [65].…”

Equine influenza

“…Τα στελέχη που απομονώθηκαν το 1993 προκαλούν πιο ήπια συμπτωματολογία από εκείνα της επιζωοτίας του 2003, παρ' όλο που ανήκουν στον ίδιο υπότυπο Η3Ν8 . Οι μελέτες έδειξαν ότι η παθογόνος δράση του ιού σχε τίζεται με την παραγωγή και απελευθέρωση κυττα-ροκινών στις αναπνευστικές εκκρίσεις και την κυκλο φορία (Wattrang et al, 2003).…”

“…Ο τίτλος των IgA και IgGa /b αντισωμάτων φαίνεται ότι φτάνει στο μέγιστο 7 έως 14 ημέρες μετά τη μόλυνση. Όμως, δύο μήνες μετά τη μόλυνση μόνο το 20% των IgA ανι χνεύεται, ενώ ο τίτλος των IgGa /b πέφτει δραματικά μετά από 15 μήνες (Wattrang et al, 2003).…”