Glycosylation clearly plays an important role in the life cycle of influenza viruses and certain glycosylation sites are required for the structural integrity and stability of the HA and NA glycoproteins during biosynthesis and formation of intact virions. Furthermore, glycosylation has been shown to modulate the functions of influenza glycoproteins, in particular the recognition of host cell receptors and in shielding antigenic epitopes on the viral HA. The addition of oligosaccharide moieties to the globular head of the HA does, however, correlate with an increased sensitivity to the antiviral activities of SP-D and to recognition and destruction of virus via the MMR on murine macrophages. Consequently, the degree of glycosylation appears to be an important factor in determining sensitivity to lectin-mediated defences, and therefore in determining the ability of a particular virus strain to replicate in the respiratory tract of mice following intranasal infection. The mouse-adapted PR8 strain which lacks mannose-containing glycans from the head of its HA molecule was largely resistant to the antiviral activities of SP-D and the MMR in vitro and induced severed clinical disease following intranasal infection of mice. The finding that mannan treatment of BJx109-infected mice facilitated an early and dramatic enhancement of disease severity is also consistent with a major role for mannose-specific lectins in limiting influenza virus growth and spread in the respiratory tract.