M1 and NEP proteins localize to the nucleus during the later stages of infection, bind to viral RNPs and mediate their export to the cytoplasm where they migrate to the cell membrane with the aid of recycled endosomes and are bundled into the segments of the genome.Progenic viruses leave the cell by budding from the cell membrane, which is initiated by the accumulation of M1 proteins at the cytoplasmic side of the membrane. The viral genome is incorporated inside a viral envelope derived from portions of the cell membrane that have HA, NA, and M2 proteins. At the end of budding, HA proteins remain attached to cellular sialic acid until they are cleaved by the sialidase activity of NA proteins. The virion is then released from the cell. The sialidase activity of NA also cleaves any sialic acid residues from the viral surface, which helps prevent newly assembled viruses from aggregating near the cell surface and improving infectivity. Similar to other aspects of influenza replication, optimal NA activity is temperature- and pH-dependent. Ultimately, presence of large quantities of viral RNA in the cell triggers apoptosis, i.e. programmed cell death, which is initiated by cellular factors to restrict viral replication. Antigenic drift and shift
Two key processes that influenza viruses evolve through are antigenic drift and antigenic shift. Antigenic drift is when an influenza viruss antigens change due to the gradual accumulation of mutations in the antigens (HA or NA) gene. This can occur in response to evolutionary pressure exerted by the host immune response.
Congenital contractural arachnodactyly (CCA), also known as Beals-Hecht syndrome, is a rare autosomal dominant congenital connective tissue disorder. As with Marfan syndrome, people with CCA typically have an arm span that is greater than their height and very long fingers and toes. However, Beals and Hecht discovered in 1972 that, unlike Marfans, CCA is caused by mutations to the fibrillin-2 (FBN2) gene rather than the fibrillin-1 (FBN1) gene. Signs and symptoms
CCA is characterized by contractures of varying degrees, mainly involving the large joints, which are present in all affected children at birth. The contractures may be mild and tend to improve over time, but permanently bent fingers and toes (camptodactyly) are almost always present. In addition to long fingers and toes and a tall, slender body, people with CCA often have ears that appear to be crumpled, joint stiffness and underdeveloped muscles (muscular hypoplasia), and they may have curved spines (congenital kyphoscoliosis). If kyphoscoliosis is present, it often becomes progressively worse and may require surgery. In some cases, the blood vessel that distributes blood from the heart to the rest of the body (aorta) may be abnormally enlarged (aortic root dilatation). Causes
Congenital contractural arachnodactyly may be the result of new mutations in the FBN2 gene or it may be inherited from a parent in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.