The heterodimeric association between the membrane proteins of Semliki Forest virus changes its sensitivity to low pH during virus maturation

Abstract

The budding and the fusion processes of the enveloped animal virus Semliki Forest virus serve the purpose of transporting its nucleocapsid, containing its genome, from the cytoplasm of an infected cell into that of an uninfected one. We show here that, in the infected cell, the viral membrane (spike) proteins p62 and El are organized as heterodimers which are very resistant to dissociation in acidic conditions. In contrast, the mature form of the heterodimer, E2E1, which is found in the virus particle and which is generated by proteolytic processing of p62, is very prone to dissociate upon treatment with mildly acidic buffers. We discuss the possibility that this difference in behavior of the intracellular precursor form and the mature form of the spike protein complex represents an important regulatory mechanism for the processes involving membrane binding around the nucleocapsid during budding and membrane release from the nucleocapsid at the stage of virus fusion.

The Murray Valley encephalitis virus prM protein confers acid resistance to virus particles and alters the expression of epitopes within the R2 domain of E glycoprotein

“…Because it has been shown with WN virus that the E and prM proteins remain as heterodimers during exocytosis (Wengler and Wengler, 1989) we reasoned that the function of the prM is to prevent conformational changes in the E glycoprotein at low pH, thus assuring safe transport of these proteins through post-Golgi acidic vesicles during maturation until the virions are released. A similar role has also been proposed for the PE2 of alphaviruses, which forms a stable dimer with the El protein (critical for infection and fusion) in the acidic compartment of the exocytic route (Lobigs and Garoff, 1990;Presley et a/., 1991;Wahlberg et al, 1989). Different approaches might be utilized by other viruses to secure the authentic expression of the envelope proteins on the infected cells.…”

Mechanism of Membrane Fusion by Viral Envelope Proteins

“…When alphavirus particles are exposed to lowered pH, protein packing in the icosahedral surface lattice changes substantially (Wahlberg et al, 1989(Wahlberg et al, , 1992. The E1-E2 heterodimers dissociate, and E1 trimerizes.…”

Structure and Working of Viral Fusion Machinery

“…All class II fusion proteins identified so far fold cotranslationally with a chaperone protein, named p62 (or pE2) for alphaviruses (Wahlberg, Boere, & Garoff, 1989) and prM (promembrane protein) for flaviviruses (Heinz et al, 1994). This heterodimeric interaction is important for the correct folding and transport of the fusion protein (Sanchez-San Martin, Liu, & ).…”

“…Structure and Working of Viral Fusion Machinery chaperone protein is cleaved by the cellular protease furin late in the secretory pathway (Stadler, Allison, Schalich, & Heinz, 1997;Zhang, Fugere, Day, & Kielian, 2003). The p62 is cleaved into E2 and E3 (Salminen, Wahlberg, Lobigs, Liljestrom, & Garoff, 1992;Wahlberg et al, 1989) and prM is cleaved into pr peptide and M protein (Heinz et al, 1994). This cleavage is crucial as it primes the protein, which is then in a metastable conformation, for subsequent low-pHinduced conformational change (Sanchez-San Martin, Liu, & Kielian, 2009).…”