Coronaviruses are enveloped RNA viruses with spike proteins, giving them a crown-like appearance. Their genetic information is carried in a single, long RNA strand. This article explains the fundamental steps coronaviruses undertake to replicate inside living cells.
Entering the Host Cell
The initial step in coronavirus replication involves gaining entry into a host cell. This process begins with the spike (S) protein, which protrudes from the viral surface. The spike protein acts like a key, specifically binding to a complementary receptor on the surface of human cells, such as the angiotensin-converting enzyme 2 (ACE2) receptor. This interaction allows the virus to infect target cells.
Upon binding, the virus can enter the host cell through one of two primary mechanisms: direct membrane fusion or endocytosis. In membrane fusion, the viral envelope merges directly with the host cell’s outer membrane, releasing the viral genetic material into the cell’s cytoplasm. Alternatively, the cell may engulf the virus through endocytosis, forming a vesicle. Inside this vesicle, the viral membrane fuses, releasing the viral RNA into the cytoplasm.
Commandeering Cellular Machinery
Immediately after entering the host cell, the viral RNA is released into the cytoplasm in a process called uncoating. This positive-sense viral RNA genome then functions directly as a messenger RNA (mRNA), instructing the host cell’s ribosomes to begin producing viral proteins. One of the first proteins translated is a large polyprotein, which is subsequently cleaved by viral proteases into multiple non-structural proteins. These non-structural proteins include the RNA-dependent RNA polymerase (RdRp), an enzyme necessary for copying its genetic material.
The RdRp, often working with other viral proteins, forms a replication-transcription complex. This complex is responsible for synthesizing new copies of the viral RNA genome and producing various subgenomic messenger RNAs. The replication process involves creating negative-strand RNA intermediates, which then serve as templates for generating full-length positive-sense genomic RNA. Subgenomic RNAs are also produced, each encoding specific viral structural or accessory proteins.
The virus effectively redirects the host cell’s resources and machinery for its own propagation. This involves utilizing the cell’s ribosomes for protein synthesis and its internal membrane systems to create specialized compartments for RNA replication. For instance, replication occurs within double-membrane vesicles, which helps shield the viral replication process from the host cell’s immune defenses. By taking over these cellular functions, the virus ensures the efficient production of all necessary components for new viral particles.
Building and Releasing New Viruses
Once the host cell has produced numerous copies of the viral RNA genome and the various viral proteins, the final stages of replication involve assembling new viral particles. This assembly process occurs within specific compartments of the host cell’s internal membrane system, particularly the endoplasmic reticulum (ER) and Golgi apparatus.
The newly synthesized viral components, including the genomic RNA, nucleocapsid proteins (which package the RNA), and the spike, membrane, and envelope structural proteins, come together in these compartments. The membrane protein (M) is important, as it drives the assembly and formation of new viral particles. The nucleocapsid, which is the viral RNA encased by N proteins, associates with the membrane proteins.
New viral particles are formed by a process called budding, where the assembled components acquire a lipid envelope from the host cell’s membranes. These newly formed virions, enclosed within vesicles, are then transported through the cell’s secretory pathway, moving towards the cell surface. Finally, these vesicles fuse with the host cell’s outer membrane, releasing the infectious virions outside the cell, ready to infect other cells and continue the cycle.