Time-related Pathological Changes in Horses Experimentally Inoculated with Equine Influenza A Virus

Abstract

To investigate the pathology of equine influenza, necropsy of 7 horses experimentally infected with equine influenza A virus (EIV) subtype H3N8 was conducted on post-infection days (PID) 2, 3, 7, and 14. Histopathologically, rhinitis or tracheitis including epithelial degeneration or necrosis with loss of ciliated epithelia and a reduction in goblet cell numbers, was observed in the respiratory tracts on PIDs 2 and 3. Epithelial hyperplasia or squamous metaplasia and suppurative bronchopneumonia with proliferation of type II pneumocytes were observed on PIDs 7 and 14. Viral antigen was detected immunohistochemically in the epithelia of the nasal mucosa, trachea, and bronchi on PIDs 2 and 3. The sodA gene of Streptococcus equi subsp. zooepidemicus , a suspected cause of suppurative bronchopneumonia, was detected in paraffin-embedded lung tissue sections, but only on PIDs 7 and 14. These findings suggest that damage caused to ciliated epithelia and goblet cells by EIV infection results in secondary bacterial bronchopneumonia due to a reduction in mucociliary clearance.

Pathology of Equine Influenza virus (H3N8) in Murine Model

“…Duration of virus shedding through nostrils in present studies (up to 5 dpi) is similar to experimental EIV infection in equines where virus could be recovered from nasal washings for a period of 5–7 dpi [ 34 – 36 , 75 , 76 ]. Similarly, from mice inoculated with eq/ROM/80, eq/GA/81 and eq/NM/03 isolates, infectious EIV was isolated from lungs and nasal turbinate up to 7 dpi [ 26 ].…”

“…Murine model has oftenly been considered as a best choice amongst small animal model to determine pathology and immune response to influenza virus infections as also for preliminary assessment of human and avian influenza vaccines [ 43 – 46 ]. Pathology of EIV infection has been studied to a greater extent in the natural host [ 34 , 47 ] where as Castleman et al . (2010), [ 25 ] while, comparing pathology of H3N8 of canine and equine origin in mice, inoculated an old lineage isolate from equines viz .…”

“…Pulmonary hepatization has been reported by Muranaka et al . (2012) [ 34 ] in equines after experimental infection with A/equine/Ibaraki/07 (H3N8; eq/IB/07) ( Table 1 ). Severe lung consolidation has been described as a pathological feature of influenza virus infection caused by the 1918 pandemic H1N1 virus and H5N1 viruses in humans [ 59 , 60 ] as well as in animal models [ 61 , 62 ].…”

“…Histological lesions in the nasal turbinate first appeared at 2 dpi and remained till 5 dpi while tracheal changes began as early as 12 hpi. Equines experimentally infected with eq/IB/07 exhibited similar degenerative lesions in the nasal turbinate and trachea [ 34 ]. Pandemic influenza virus infection in humans [ 63 ], H1N1 and H3N2 in guinea pigs [ 64 ], classical swine H1N1 in ferrets and mice [ 65 ], HPAI H5N1 in mice [ 48 ] resulted in comparable lesions and antigen distribution as observed in our studies.…”

“…Our findings with regard to antigen distribution and ultra structural changes are in conformity with the observation of Castleman et al (2010) [ 25 ] in mice and canines infected with A/canine/Florida/04. Experimental infection in equines with eq/IB/07 produced lesions of bronchopneumonia in second phase of febrile illness, while horses naturally infected with A/equine/Sydney/07 showed lesions of proliferative tracheitis, bronchointerstitial pneumonia and bacterial bronchopneumonia ( Table 1 ) [ 34 , 42 ]. Lesions in lungs of mice were comparable to host species with minor differences such as presence of more interstitial, alveolar, bronchiolar changes and early inflammatory cellular responses in mice, which can be explained in relation to differences in localization of receptors for binding of HA molecule for various species.…”