Viruses are microscopic entities that cannot reproduce on their own; instead, they must infiltrate a host cell to hijack its machinery for replication. Entry into a host cell is a fundamental process in the viral life cycle. Understanding how viruses access cells is crucial for comprehending infections and developing combat strategies. The mechanisms viruses employ for entry are diverse, reflecting their adaptation to different host cells and environments.
Primary Viral Entry Routes
Many viruses initiate infection by attaching to specific molecules, known as receptors, on the surface of host cells. This attachment is a highly selective process, determining which cells a virus can infect. Following attachment, enveloped viruses, encased in a host-derived lipid membrane, often enter through direct membrane fusion. The viral envelope merges with the host cell’s outer membrane, releasing genetic material directly into the cell. Viruses like HIV utilize this direct fusion mechanism.
Another common entry pathway for both enveloped and non-enveloped viruses is receptor-mediated endocytosis. After binding to cell surface receptors, the host cell engulfs the virus by forming a small membrane pocket that pinches off to create an internal vesicle. This internal compartment, an endosome, often acidifies. This acidity triggers structural changes in viral proteins, releasing genetic material into the cell’s cytoplasm. Influenza virus, for example, enters cells this way, with genetic material released from acidified endosomes.
Beyond Standard Endocytosis: Macropinocytosis
While receptor-mediated endocytosis is a highly specific process, some viruses employ a less selective, bulk uptake mechanism called macropinocytosis. Unlike typical endocytosis, which uses specific receptors and forms small vesicles, macropinocytosis involves the cell “gulping” large amounts of extracellular fluid and suspended particles, including viruses. This process begins with ruffling or blebbing of the cell’s outer membrane, driven by the actin cytoskeleton. These protrusions close, forming large, irregular vacuoles called macropinosomes that internalize fluid and viruses.
Viruses such as adenovirus, vaccinia virus, and Ebola virus exploit macropinocytosis for entry. This pathway allows viruses to bypass the strict requirement for specific receptors that trigger other endocytosis forms. By inducing macropinocytosis, viruses can be non-specifically internalized, increasing their chances of infecting a cell even if specific receptors are scarce or absent. Filamentous influenza virus forms, too large for typical clathrin-mediated endocytosis, primarily use macropinocytosis for entry.
Cell-to-Cell Spread: Bypassing Extracellular Release
Beyond entering individual cells, viruses can spread directly from an infected cell to an uninfected neighbor without extracellular release. This cell-to-cell transmission offers an advantage by allowing viruses to evade immune detection and neutralization, particularly by circulating antibodies, significantly enhancing viral propagation within a tissue or organism.
One mechanism for direct cell-to-cell spread is the formation of a “virological synapse.” This specialized, transient junction forms between infected and target cells, acting as a bridge for efficient viral transfer. Viruses like HIV and human T-lymphotropic virus (HTLV) utilize virological synapses, concentrating viral particles and cellular machinery at the contact point to facilitate direct passage. Another method involves the fusion of an infected cell with an uninfected cell, creating a large, multinucleated syncytium. Viruses such as measles virus and respiratory syncytial virus (RSV) induce syncytia, enabling spread to many adjacent cells while protected from immune response.