Background:  The entry of enveloped viruses into host cells is mediated by viral envelope glycoproteins. The fusion of the viral and target cell membranes is driven by conformational changes in the envelope glycoproteins triggered by acidic environment in the endosomal body for “pH-dependent viruses” and by receptor binding for “pH-independent viruses.” Influenza A virus is the prototype of pH-dependent viruses, and HIV-1 and amphotropic murine leukemia virus (A-MLV) are examples of pH-independent viruses.  

Methods:  By titrating dominant-negative mutants into the envelope glycoprotein trimers of these viruses, we determined the number (T) of trimers required for successful virus entry.

Results:  Influenza A virus needs approximately 8 to 9 hemagglutinin trimers to function cooperatively to mediate virus–cell membrane fusion and virus entry. Surprisingly, for HIV-1 and A-MLV, a single envelope glycoprotein trimer can independently support virus entry. 

Conclusions:  Thus, entry of distinct viruses requires markedly different degrees of cooperation among the envelope spikes, which has important implications in viral replication and pathogenesis.

Keywords: stoichiometry; hiv; infleunza A virus