1996 Abstracts The American Pediatric Society and The Society for Pediatric Research | Published:


Human parainfluenza viruses types 1, 2 and 3 (HPF 1, 2 & 3) are important pathogens in children. While these viruses share common structural features and replication strategies, they target different parts of the respiratory tract; the most common outcomes of infection with HPF3 are bronchiolitis and pneumonia, while HPF1 and 2 are associated with the croup syndrome. The envelope of these viruses contains two viral glycoproteins, the receptor binding protein, hemagglutinin-neuraminidase (HN) and the fusion protein (F). While F is critical for membrane fusion, our previous work revealed that for HPF3, the HN is also essential to the fusion process; interaction between HN and its sialic acid-containing receptor on cell surfaces is required for HPF3-mediated cell fusion. Using our understanding of the functions of the HPF3 HN molecule in the cell-binding and viral entry process, we are investigating the ways in which these processes differ in HPF types 1 and 2. To investigate the sialic acid receptor requirements for HPF1- and 2- mediated cell-cell fusion, we manipulated receptor availability. Three experimental treatments were used to compare the HN-receptor interaction of HPF 1, 2 and 3: infection at high multiplicity of infection (m.o.i.), bacterial neuraminidase treatment of cells infected at low m.o.i. and viral neuraminidase treatment of cells infected at low m.o.i. (using Newcastle disease virus [NDV] neuraminidase or UV-irradiated HPF3 as sources of viral neuraminidase.) In cells infected with HPF3, we have shown that infection with high m.o.i. blocks fusion, by removing sialic acid receptors for the viral HN; however, in cells infected with HPF1 and HPF2, infection with high m.o.i. did not block fusion; the fusion increases with increasing multiplicity. In cells infected with HPF1 and HPF2, neither bacterial neuraminidase nor NDV neuraminidase blocked cell fusion, using amounts of neuraminidase that completely block fusion of HPF3-infected cells. However, when inactivated HPF3 was used as a source of viral neuraminidase (in amounts to simulate a high m.o.i.), the treatment inhibited fusion of cells infected with HPF 1, 2 and 3. Thus, for HPF1 and 2, cell fusion is not blocked by either high multiplicity infection or by bacterial or NDV neuraminidase treatment, but is partially blocked by inactivated HPF3. These viruses thus differ in their interaction with the host cell, their ability to modulate cell-cell fusion and the effects of exogenous neuraminidases of various specificities on this process. Further experiments are underway to characterize the precise nature of the receptor interaction for each of the three viruses. These studies may shed light on the molecular mechanism whereby the human parainfluenza viruses cause different spectra of disease in children.

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