Pathogenesis of a Chinese strain of bovine adenovirus type 3 infection in albino guinea pigs

Abstract

Bovine adenovirus type 3 (BAV-3) is considered one of the most important respiratory tract agents of cattle and is widespread among cattle around the world. A BAV-3 strain was isolated from a bovine nasal swab for the first time in China in 2009 and named HLJ0955. Subsequently, BAV-3 has frequently been isolated from calves with respiratory diseases in China. To date, only limited study on the pathogenesis of BAV-3 infection in cotton rats has been conducted, and the pathogenesis of BAV-3 infection in guinea pigs has not been reported. Therefore, sixteen albino guinea pigs were inoculated intranasally with HLJ0955. All of the infected guinea pigs had apparently elevated rectal temperatures (39.2 °C-39.9 °C) at 2-7 days post-inoculation (PI). Consolidation and petechial hemorrhage were also observed in guinea pigs experimentally infected with HLJ0955. Viral replication was detectable by virus isolation and titration and by immunohistochemistry in the lungs of guinea pigs as early as 24 h PI. Viral DNA was detectable in the lungs of infected guinea pigs during 11 days of observation by real-time PCR. Virus-neutralizing antibodies against BAV-3 were detectable from 11 days PI and reached a peak titer at 15 days PI. Histopathological changes mainly occurred in the lungs of infected guinea pigs and were characterized by thickening of alveolar septa, mononuclear cell infiltration, hemorrhage and alveolar epithelial necrosis. These results indicate that HLJ0955 can replicate in the lungs of guinea pigs and cause fever and gross and histological lesions. The guinea pig infection model of BAV-3 would serve as a useful system for monitoring the infection process and pathogenesis of the Chinese BAV-3 strain HLJ0955, as well as immune responses to BAV-3 vaccines.

Pathogenicity of a novel bovine adenovirus type 3 with a natural deletion partial fiber gene in BALB/c mice

“…The results of viral titers and viral loads were summarized in Supplementary Table S1 and line graphs were constructed based on the data ( Figure 6 ). Unlike previous reports where the virus could only be detected in the lungs and trachea ( 22 , 23 ), in this study it was detected in multiple organs and even in the blood throughout the infection period. With the exception of the trachea and blood, the replication of the virus in all organs showed a certain regularity, reaching the highest viral titers and viral loads on a given day and then gradually decreasing.…”

“…Subsequently, the replication kinetics of the virus in various tissues and organs was detected. The results of virus titration and qPCR showed that the virus could be detected as early as 24 h after infection, and maintained high viral loads from 1 to 15 days, with a much longer duration of infection than previously reported for HLJ0955 strain (22,23). In addition, the virus could infect and replicate in various organs, such as heart, liver, spleen, lung, kidney, trachea and even blood, which was different from the previous report that the virus replicated only in the lung and trachea (22)(23)(24), indicating that the virus tissue tropism has been altered and can cause viremia.…”

“…The results of virus titration and qPCR showed that the virus could be detected as early as 24 h after infection, and maintained high viral loads from 1 to 15 days, with a much longer duration of infection than previously reported for HLJ0955 strain (22,23). In addition, the virus could infect and replicate in various organs, such as heart, liver, spleen, lung, kidney, trachea and even blood, which was different from the previous report that the virus replicated only in the lung and trachea (22)(23)(24), indicating that the virus tissue tropism has been altered and can cause viremia. This may be related to the deletion of the fiber shaft domain, which has been previously shown to play a decisive role in viral tissue tropism and immune evasion by the length of the shaft domain and the variation of the knob domain (20,21,27,28).…”

“…Mitta et al intranasally inoculated BAdV-3 into cotton rats and found that the virus was able to undergo limited replication in the lungs and trachea, consistent with the symptoms of BAdV-3 infection in cattle ( 24 ). Shi Hongfei et al studied the pathogenicity of Chinese BAdV-3 strain HLJ0955 by intranasal inoculation into BALB/c mice and guinea pigs and found that the infection model would serve as a useful system for monitoring the infection process and pathogenesis ( 22 , 23 ). These suggest that SPF experimental animals are feasible as an animal model to study BAdV-3.…”

Recombinant hexon protein as a new bovine adenovirus type 3 subunit vaccine candidate

“…Bovine adenoviruses (BAdVs) are involved in the bovine respiratory disease complex and are a cause of significant economic losses in the beef and dairy industries ( 9 , 23 ). The ten known BAdV serotypes are divided into two groups based on viral neutralization tests.…”