Function

The HCV particles are spherical and heterogenous in size, ranging 40-80 nm in diameter. This cross-sectional view of the HCV particle shows all of the viral elements: the envelope glycoproteins (E1 and E2 heterodimers), a lipid membrane, the nucleocapsid, and the single-stranded RNA genome.

Function

The HCV envelope glycoproteins consist of the E1 and E2 glycoproteins noncovalently associated as a heterodimer. This E1/E2 glycoprotein heterodimer is embedded in the host-derived lipid membrane and together forms the HCV envelope. The envelope glycoproteins form a higher order oligomeric structure consisting of trimers of E1/E2 heterodimers (three groups of heterodimers); the trimers can then assemble into pentamers (five groups of trimers). Structurally, the hypervariable region in the E2 protein shields the E1 protein from the immune system. The envelope proteins play a role in host receptor binding, endosome-lipid membrane fusion, and assembly. The E1 protein is approximately 192 amino acids long and the E2 protein is approximately 363 amino acids long. The host-derived lipid membrane component of the envelope is composed primarily of cholesterol, cholesteryl esters, phosphatidylcholine, and sphingomyelin.

Function

The HCV lipid membrane is composed primarily of cholesterol, cholesteryl esters, phosphatidylcholine, and sphingomyelin. The cholesterol content of the HCV particle is higher when compared with host cell membranes. The HCV membrane has a very high amount of incorporated cholesterol, which gives it a composition that resembles human very-low-density lipoprotein (VLDL). The specific ratios of lipids in HCV membranes clearly distinguishes it from other viruses and from host cells. It appears that cholesterol and sphingolipid both play a role in the entry of HCV into host cells.

Function

The HCV capsid, also known as the HCV core, is the protein shell that encapsidates and protects the HCV RNA. The HCV capsid is made up entirely by the HCV core protein. The proteins on the outer surface of the core interact with the viral membrane and inner surface binds to several HCV RNA segments. Following cleavage from the polypeptide, the core proteins assemble at the cytoplasmic face of the endoplasmic reticulum to form the capsid; this assembly process is triggered by interactions with the HCV RNA and envelope E1 protein. During assembly the core proteins use the HCV RNA as a scaffold upon which core proteins bind to and surround the HCV RNA. The HCV capsid is spherical and heterogenous in size, with an approximate diameter of 30 nm.

Function

The HCV nucleocapsid consists of the HCV capsid plus the HCV RNA. The capsid, which consists entirely of HCV core proteins, forms a shell that encapsidates and protects the HCV RNA. The HCV RNA is single-stranded, positive-sense RNA that is approximately 9,600 nucleotide bases in length. Certain segments of the HCV RNA bind to the capsid structure. The HCV nucleocapsid is spherical and heterogenous in size, with an approximate diameter of 30 nm.

Function

The HCV RNA (genome) consists of a single-stranded, positive-sense RNA approximately 9,600 nucleotide bases in length. The HCV genome contains a single, long, open reading frame (3,006-3037 codons) flanked by 5' and 3' untranslated regions (UTRs). The HCV RNA genome is used both for translation and transcription. The 5' region, which is upstream from the open reading frame, is approximately 340 nucleotides long and contains 4 highly structured domains: domain I consists of a short stem loop and domains II-IV form the internal ribosomal entry site (IRES). The IRES is a highly structured regulatory element that mediates binding of the HCV RNA to the host ribosomal subunits (and cellular factors), which is essential in the translation of the open reading frame. The 3' region is approximately 225 nucleotides long and it consists of three components: variable, a long poly (U/UC) tract, and 3'X region. The 3'X region serves as a key factor in switching between translation and RNA transcription of the HCV RNA.

Function

In the bloodstream, HCV can circulate as a hybrid lipoviral particle that consists of lipoproteins tightly associated with the HCV particle. The specific components of the lipoviral particle include triglycerides, HCV RNA, capsid protein, E1 envelope glycoprotein, E2 envelope glycoprotein, apolipoprotein B, and apolipoprotein E. The diameter of these lipoviral particles is approximately 100 nm.  The formation of the lipoviral particle facilitates HCV entry into hepatocytes and it protects HCV from antibody neutralization. The density of these lipoviral particles is similar to low-density lipoproteins (LDLs) and very-low-density lipoproteins (VLDLs) that normally circulate in the bloodstream.