Highly pathogenic avian influenza virus (HPAIV) from the H5N1 subtype continues to be reported to infect pigeons asymptomatically or induce mild symptoms. the lungs contaminated TG-101348 with Pigeon04 aswell as T.sparrow05 through the entire collection intervals. Encephalitis was sometimes seen in Pigeon04- or T.sparrow05-contaminated brain, the severe nature, TG-101348 was mostly mild however. To analyze the expression of immune-related genes in the infected pigeons, we established a quantitative real-time PCR analysis for 14 genes of pigeons. On day 2 post infection, Pigeon04 induced mRNA expression of Mx1, PKR and OAS to a greater extent than T.sparrow05 in the lungs, however their expressions were not up-regulated concomitantly on day 5 post infection when the peak viral replication was observed. Expressions of TLR3, IFN, IL6, IL8 and CCL5 in the lungs following infection with the two HPAIVs were low. In sum, Pigeon04 exhibited efficient replication in the lungs compared to T.sparrow05, but did not induce excessive host cytokine expressions. TG-101348 Our study has provided the first insight into host immune responses of pigeons against HPAIV infection. Introduction The highly pathogenic avian influenza virus (HPAIV) of subtype H5N1, that is currently spread worldwide was first isolated from domestic goose in Guangdong Province, China in 1996 [1]. The following year, sporadic outbreaks of H5N1 HPAIVs occurred in poultries across Hong Kong and were accompanied by human infections that resulted in the deaths of 6 of 18 Hong Kong residents infected with the virus [2]. HPAIVs were thought to cause lethal infections only in gallinaceous birds such as chickens, but not in domestic and wild waterfowls. In late 2002, however, H5N1 HPAIV outbreaks in Hong Kong occurred in waterfowls and wild birds, resulting in the deaths of many resident avian species including ducks, geese, swans, pigeons and tree sparrows [3]. These H5N1 HPAIVs, however, were reported to differ antigenetically from those isolated between 1997 and 2001, and were lethal to ducks in a laboratory experiment [4]. In 2005, H5N1 HPAI outbreaks in wild migratory waterfowls that occurred at Qinghai Lake, China, led to the die-off of migratory birds [5]. In Thailand, HPAIVs were isolated from mammalian species including tigers, leopards, dogs and cats and wild birds including open-bill storks, pigeons and tree TG-101348 sparrows during the HPAI outbreaks in poultries in 2004C2005 [6]C[11]. The Asian H5N1 HPAIVs isolated from humans in 2004 have been reported to have increased pathogenicity Rabbit polyclonal to PPA1 in ferrets compared to HPAIVs isolated in 1997 [12]. These reports suggest that current HPAIVs appear to be more lethal to mammals and wild birds compared to those isolated before 2001. There are several reports on the virulent mechanisms of HPAIVs in birds, particularly chickens. Virulent H5N1 HPAIV, but not avirulent virus, was reported to inhibit mRNA expression of IFN/ in chick embryonated cells. This indicated that the pathogenicity of HPAIVs in chickens is influenced by their ability to antagonize host IFN responses [13], [14]. Wasilenko et al demonstrated that earlier death of chickens infected with H5N1 HPAIVs was associated with efficient viral replication in the lungs and spleens accompanied by up-regulation of antiviral cytokines such as IFN, IFN and orthomyxovirus resistance gene 1 (Mx1) [15]. Suzuki et al compared host cytokine responses towards two H5N1 HPAIVs with different mean death times (MDT) in virus infected chickens [16]. They suggested that efficient viral replication accompanied by destruction of innate immune responses in chickens contributed to increased pathogenecity of the HPAIVs. Barber et al reported the relationship between influenza virus sensor RIG-I and virulence of H5N1 HPAIV in ducks, which are believed to be more resistant to HPAIV infection than chickens [17]. They demonstrated.