Viruses with approximately 50% homology to human influenza C virus (ICV) have recently been isolated from swine and cattle. The overall low homology to ICV, lack of antibody cross-reactivity to ICV in hemagglutination inhibition (HI) and agar gel immunodiffusion assays, and inability to productively reassort with ICV led to the proposal that these viruses Influenza viruses are single-stranded, negative-sense, segmented RNA viruses belonging to the family Orthomyxoviridae (1). Influenza A virus (IAV) and influenza B virus (IBV) both contain eight genomic segments, including two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), whereas influenza C (ICV) has only seven segments with one surface glycoprotein, the hemagglutinin-esterase-fusion (HEF) protein (2, 3). While the vast genetic diversity of IAV is found in waterfowl, only limited subtypes infect mammals. IBV and ICV are found principally in humans and rarely infect other species. IBV is a component of seasonal influenza epidemics with clinically significant disease, while ICV infects most humans during childhood and typically results in mild respiratory symptoms and fever (1, 4 -6).In 2011

Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.

Influenza Influenza viruses are classified as genera A, B, and C, in accordance with the antigenic differences in their nucleoproteins (NP) and matrix 1 (M1) proteins (28). Influenza A (IAV) and B (IBV) viruses can result in severe upper respiratory disease in humans, while influenza C viruses (ICV) cause relatively mild disease (9, 23). Among influenza viruses, IAV and IBV are very similar in terms of genome structure and organization. IBV, along with influenza A(H3N2) and A(H1N1) viruses [including A(H1N1)pdm09 virus], cause seasonal influenza epidemics annually (9, 23). In the United States alone during 1976 to 2007, approximately 3,000 to 49,000 deaths each year have been attributed to these epidemics (42). Some reports indicate that in older children and healthy adults, influenza A(H3N2) virus is responsible for the most severe cases, followed by IBV, while influenza A(H1N1) virus infections tend to manifest as the mildest cases of illness (1,5,23,25). In some seasons, however, IBV may be the predominate strain responsible for influenza activities. This was best exemplified by the 1979-1980 season, in which IBV was the predominant strain circulating in the United States; therefore, it was responsible for influenza outbreaks and excess pneumonia and influenza deaths nationwide (39). Furthermore, IBV has been reported to be associated with central nervous system complications, such as Reye's syndrome and encephalitis in children (1).IBVs continue to circulate worldwide alongside IAVs. Actively circulating IBVs are divided into two genetically and antigenically

Rift Valley fever (RVF) is a zoonotic disease that causes severe epizootics in ruminants, characterized by mass abortion and high mortality rates in younger animals. The development of a reliable challenge model is an important prerequisite for evaluation of existing and novel vaccines. A study aimed at comparing the pathogenesis of RVF virus infection in US sheep using two genetically different wild type strains of the virus (SA01-1322 and Kenya-128B-15) was performed. A group of sheep was inoculated with both strains and all infected sheep manifested early-onset viremia accompanied by a transient increase in temperatures. The Kenya-128B-15 strain manifested higher virulence compared to SA01-1322 by inducing more severe liver damage, and longer and higher viremia. Genome sequence analysis revealed sequence variations between the two isolates, which potentially could account for the observed phenotypic differences. We conclude that Kenya-128B-15 sheep infection represents a good and virulent challenge model for RVF.

Although several studies have investigated the functions of influenza PA-X, the impact of different expressions of PA-X protein including full-length, truncated or PA-X deficient forms on virus replication, pathogenicity and host response remains unclear. Herein, we generated two mutated viruses expressing a full-length or deficient PA-X protein based on the A/California/04/2009 (H1N1) virus that expresses a truncated PA-X to understand three different expressions of PA-X protein on virus replication, pathogenicity and host immune responses. The results showed that expression of either full-length or truncated PA-X protein enhanced viral replication and pathogenicity as well as reduced host innate immune response in mice by host shutoff activity when compared to the virus expressing the deficient PA-X form. Furthermore, the full-length PA-X expression exhibited a greater effect on virus pathogenicity than the truncated PA-X form. Our results provide novel insights of PA-X on viral replication, pathogenicity and host immune responses.