active form, F1 and F2, linked by di-sulphide bonds. Once complete, this is followed by the HPIV nucleocapsid entering the cytoplasm of the cell. Subsequently, genomic transcription occurs using the viruses own 'viral RNA-dependent RNA polymerase' (L protein). The cell's own ribosomes are then tasked with translation, forming the viral proteins from the viral mRNA. Towards the end of the process, (after the formation of the viral proteins) the replication of the viral genome occurs. Initially, this occurs with the formation of a positive-sense RNA (intermediate step, necessary for producing progeny), and finally, negative-sense RNA is formed which is then associated with the nucleoprotein. This may then be either packaged and released from the cell by budding or used for subsequent rounds of transcription and replication. The observable and morphological changes that can be seen in infected cells include the enlargement of the cytoplasm, decreased mitotic activity and 'focal rounding', with the potential formation of multi-nucleate cells (syncytia). The pathogenicity of HPIVs is mutually dependent on the viruses having the correct accessory proteins that are able to elicit anti-interferon properties. This is a major factor in the clinical significance of disease. Host range The main host remains the human. However, infections have been induced in other animals (both under natural and experimental situations), although these were always asymptomatic. Clinical significance It is estimated that there are 5 million children with lower respiratory infections (LRI) each year in the United States alone. HPIV-1, HPIV-2 and HPIV-3 have been linked with up to a third of these infections. Upper respiratory infections (URI) are also important in the context of HPIV, however, they are caused to a lesser extent by the virus. The highest rates of serious HPIV illnesses occur among young children, and surveys have shown that about 75% of children aged 5 or older have antibodies to HPIV-1. For infants and young children, it has been estimated that about 25% will develop "clinically significant disease". Repeated infection throughout the life of the host is not uncommon and symptoms of later breakouts include upper respiratory tract illness, such as cold and a sore throat. The incubation period for all four serotypes is 1 to 7 days. In immunosuppressed people, parainfluenza virus infections can cause severe pneumonia, which can be fatal. HPIV-1 and HPIV-2 have been demonstrated to be the principal causative agent behind croup (laryngotracheobronchitis), which is a viral disease of the