RNA enveloped viruses comprise several families belonging to plus and minus strand RNA viruses, such as retroviruses, flavoviruses and orthomyxoviruses. Viruses utilize cellular lipids during critical steps of replication like entry, assembly and egress. Growing evidence indicate important roles for lipids and lipid nanodomains in virus assembly. The proposed topic will cover key aspects of virus-membrane interactions during assembly and egress. A significant part of this special topic will address how enveloped viruses such as retroviruses, influenza, Ebola and Dengue viruses are able to recognize specific lipids in membrane during assembly and egress. Virus assembly and release involve specific and nonspecific interactions between viral proteins and membrane compartments. It is well established that assembly of retroviral Gag proteins occur predominantly on the PM. Membrane selection appears to be critical for productive virus production. Gaps in understanding of retroviral assembly still exist. Studies have provided compelling evidence that localization of HIV-1 Gag on the PM is critically dependent on phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), a minor phospholipid localized on the inner leaflet of the plasma membrane. Structural studies have subsequently shown that PI(4,5)P2 binds directly to HIV-1 MA, inducing a conformational change that triggers myr exposure. These results were recapitulated for HIV-2. Other studies have focused whether retroviruses in general utilize a similar mechanism. It appears that several retroviruses like Rous sarcoma virus (RSV), equine infectious anemia virus (EIAV), Mason-Pfizer monkey virus (MPMV), and human T-lymphotropic virus type (HTLV-1) may have evolved different or similar mechanisms for membrane targeting and assembly. Most recent studies from Volker Vogt lab indicate that efficient binding of HIV-1 and RSV Gag and MA proteins is not only dependent on inclusion of PI(4,5)P2 or nature of phospholipid (PS vs. PC), but is also sensitive to the hydrophobic environment of the bilayer (acyl chains and cholesterol). In addition, other studies from Muriaux’s lab have shown that the MA domain of MLV also recognize specifically the PI(4,5)P2 at the PM, only highly enhanced by the presence of PS. In the most recent study (PNAS, in press), the Saad lab has shown that PS, PE, and PC interact directly with MA via a region that is distinct from the PI(4,5)P2 binding site. Structural data also show that the myristate (myr) group is readily exposed when MA is bound to micelles or bicelles. Altogether, these findings shed light on a potential new role for major PM phospholipids and may provide new insight into a possible alternative mechanism for Gag assembly in retroviruses lacking the myr group or PI(4,5)P2 requirement.
Influenza viruses also possess a lipid membrane derived from the host cell, harboring the envelope glycoproteins hemagglutinin (HA), the neuraminidase (NA), M1 and some of the M2 proteins, which act as budding proteins. Assembly and budding of influenza viruses appear to proceed in the viral budozone, a domain in the plasma membrane with characteristics of cholesterol/sphingolipid-rich membrane rafts. Likewise, compartmentalization of viral proteins within lipid rafts has been observed during assembly and budding of Ebola and Marburg viruses. It is our expectation that this special topic will cover a range of scientific topics that will certainly be of interest for many readers.
RNA enveloped viruses comprise several families belonging to plus and minus strand RNA viruses, such as retroviruses, flavoviruses and orthomyxoviruses. Viruses utilize cellular lipids during critical steps of replication like entry, assembly and egress. Growing evidence indicate important roles for lipids and lipid nanodomains in virus assembly. The proposed topic will cover key aspects of virus-membrane interactions during assembly and egress. A significant part of this special topic will address how enveloped viruses such as retroviruses, influenza, Ebola and Dengue viruses are able to recognize specific lipids in membrane during assembly and egress. Virus assembly and release involve specific and nonspecific interactions between viral proteins and membrane compartments. It is well established that assembly of retroviral Gag proteins occur predominantly on the PM. Membrane selection appears to be critical for productive virus production. Gaps in understanding of retroviral assembly still exist. Studies have provided compelling evidence that localization of HIV-1 Gag on the PM is critically dependent on phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), a minor phospholipid localized on the inner leaflet of the plasma membrane. Structural studies have subsequently shown that PI(4,5)P2 binds directly to HIV-1 MA, inducing a conformational change that triggers myr exposure. These results were recapitulated for HIV-2. Other studies have focused whether retroviruses in general utilize a similar mechanism. It appears that several retroviruses like Rous sarcoma virus (RSV), equine infectious anemia virus (EIAV), Mason-Pfizer monkey virus (MPMV), and human T-lymphotropic virus type (HTLV-1) may have evolved different or similar mechanisms for membrane targeting and assembly. Most recent studies from Volker Vogt lab indicate that efficient binding of HIV-1 and RSV Gag and MA proteins is not only dependent on inclusion of PI(4,5)P2 or nature of phospholipid (PS vs. PC), but is also sensitive to the hydrophobic environment of the bilayer (acyl chains and cholesterol). In addition, other studies from Muriaux’s lab have shown that the MA domain of MLV also recognize specifically the PI(4,5)P2 at the PM, only highly enhanced by the presence of PS. In the most recent study (PNAS, in press), the Saad lab has shown that PS, PE, and PC interact directly with MA via a region that is distinct from the PI(4,5)P2 binding site. Structural data also show that the myristate (myr) group is readily exposed when MA is bound to micelles or bicelles. Altogether, these findings shed light on a potential new role for major PM phospholipids and may provide new insight into a possible alternative mechanism for Gag assembly in retroviruses lacking the myr group or PI(4,5)P2 requirement.
Influenza viruses also possess a lipid membrane derived from the host cell, harboring the envelope glycoproteins hemagglutinin (HA), the neuraminidase (NA), M1 and some of the M2 proteins, which act as budding proteins. Assembly and budding of influenza viruses appear to proceed in the viral budozone, a domain in the plasma membrane with characteristics of cholesterol/sphingolipid-rich membrane rafts. Likewise, compartmentalization of viral proteins within lipid rafts has been observed during assembly and budding of Ebola and Marburg viruses. It is our expectation that this special topic will cover a range of scientific topics that will certainly be of interest for many readers.
