Influenza, commonly known as the flu, is a respiratory illness caused by the influenza virus. Understanding how this virus interacts with human cells is fundamental to comprehending flu symptoms and disease progression.
Understanding the Influenza Virus
The influenza virus is an enveloped virus, meaning it has an outer lipid membrane derived from the host cell. This spherical particle houses its genetic material, consisting of eight single-stranded RNA segments. These segments are negative-sense, meaning they cannot be directly translated into proteins.
The viral envelope is studded with glycoprotein spikes, primarily hemagglutinin (HA) and neuraminidase (NA), which are important for infection. Influenza A and B are the primary causes of human epidemics.
How Influenza Invades and Takes Over a Cell
The infection process begins with the influenza virus attaching to a host cell. Hemagglutinin (HA) proteins on the viral surface bind to sialic acid receptors on the outer membrane of respiratory cells. This binding initiates internalization, where the host cell engulfs the virus.
The cell “swallows” the virus through endocytosis, forming an endosome around the viral particle. The endosome then travels deeper into the cell, and its internal environment becomes more acidic. This acidic shift triggers a conformational change in the HA protein.
The change in HA’s structure facilitates the fusion of the viral envelope with the endosomal membrane. This fusion is followed by uncoating, releasing the viral genetic material (ribonucleoprotein, or RNP, complexes containing the viral RNA segments) into the host cell’s cytoplasm. The viral RNPs then travel to the cell’s nucleus.
Once inside the nucleus, the influenza virus hijacks the host cell’s machinery. The viral RNA-dependent RNA polymerase (RdRP) takes over the cell’s transcription and replication processes. This viral polymerase performs “cap snatching,” cleaving the 5′ cap from host messenger RNAs (mRNAs) and using these fragments as primers to initiate transcription of its own viral mRNAs. This enables the virus to produce its proteins and replicate its genome.
Creating New Viruses and Spreading
After viral genetic material is replicated and viral proteins synthesized, new virus particles assemble. The newly made viral RNA segments, along with nucleoproteins and the viral polymerase, form new ribonucleoprotein (RNP) complexes. These RNPs are then exported from the nucleus to the cytoplasm.
The viral envelope proteins, HA and NA, are transported through the cell’s internal membrane system to the plasma membrane. These viral proteins cluster together. The matrix protein (M1) then associates with the cytoplasmic tails of HA and NA, forming an inner shell beneath the membrane.
This assembly draws the newly formed RNPs to the budding site. Budding involves the outward protrusion of the host cell’s membrane, encapsulating the assembled viral components. The viral M2 ion channel protein helps alter membrane curvature and facilitates the final pinching off of the new virus particle from the host cell.
The newly released influenza virions acquire a piece of the host cell’s membrane as their outer envelope. Neuraminidase (NA) proteins on the surface of the new virus particles help release them from the infected cell by cleaving sialic acid receptors, allowing the viruses to spread. These viruses are then free to infect neighboring cells or be transmitted to others through respiratory droplets, continuing the infection cycle.
The Cell’s Fight and the Body’s Response
Intensive viral replication within an infected cell damages its resources. The hijacking of cellular machinery and production of viral components often lead to the infected cell’s death, a process known as apoptosis. This cellular destruction contributes to tissue damage during influenza infection.
The presence of infected cells and viral particles triggers a strong response from the body’s immune system. This includes the release of signaling molecules called cytokines, which can lead to inflammation, fever, and muscle aches. These symptoms are the body’s attempt to fight off the infection.
Specialized immune cells, such as natural killer (NK) cells and T-cells, combat the infection. NK cells identify and destroy virus-infected cells early, limiting viral spread by inducing apoptosis. T-cells also target and eliminate infected cells, contributing to viral clearance. However, in some cases, the immune response can be overly aggressive, leading to excessive inflammation and tissue damage, sometimes referred to as a “cytokine storm,” which can contribute to severe illness.