Membrane Uncoating of Intact Enveloped Viruses

Experiments in the 1960s showed that Sendai virus, a paramyxovirus, fused its membrane with the host plasma membrane. After membrane fusion, the virus spontaneously “uncoated” with diffusion of the viral membrane proteins into the host plasma membrane and a merging of the host and viral membranes. This led to deposit of the viral ribonucleoprotein (RNP) and interior proteins in the cell cytoplasm. Later work showed that the common procedure then used to grow Sendai virus produced damaged, pleomorphic virions. Virions, which were grown under conditions that were not damaging, made a connecting structure between virus and cell at the region where the fusion occurred. The virus did not release its membrane proteins into the host membrane. The viral RNP was seen in the connecting structure in some cases. Uncoating of intact Sendai virus proceeds differently from uncoating described by the current standard model developed long ago with damaged virus. A model of intact paramyxovirus uncoating is presented and compared to what is known about the uncoating of other viruses.Enveloped virus entry at the plasma membrane includes binding of the virion to one or more receptors, changes in the virion components, membrane fusion, and membrane uncoating. The term “membrane uncoating” is being used to describe the separation of internal virion components from the viral membrane so the internal components can enter the cell. The term “uncoating” is sometimes used to mean the release of the viral genome from the capsid or other structures that have also entered the cell, but in this review, the term “membrane uncoating” will be used to represent only the separation of the virion internal contents and the viral envelope.Much of the original model of membrane fusion and uncoating was generally accepted as a result of a 1968 paper by Morgan and Howe (41). That paper provided strong evidence that Sendai virus (a paramyxovirus) entered a cell by fusion of the viral membrane with the cell plasma membrane. After membrane fusion, the virion rapidly lost its structure as the viral membrane merged with the host membrane and its components became part of the host membrane. The viral ribonucleoprotein (RNP) and internal proteins were released into the cytoplasm. This model of membrane uncoating is still generally accepted. For instance, in a 2007 virology text (24), this model was presented and illustrated with a figure from the Morgan and Howe paper. (The same figure is shown here as Fig. 2B.)Later, it was shown that Sendai viruses, which had been grown in fertilized chicken eggs, had different properties depending whether they had been harvested after growth for roughly 1 day (“early harvest”) or for several days (“late harvest”). The early-harvest viruses appear to be intact, but the late-harvest viruses have a different morphology and appear to be damaged (20, 26).This review summarizes data showing that intact early-harvest Sendai viruses uncoat quite differently from the way damaged late-harvest Sendai viruses uncoat. A model of intact paramyxovirus membrane uncoating is presented. The membrane uncoating of some other enveloped viruses that enter at the plasma membrane is compared to that described by this model.