The Measles Virus (MeV) is a highly contagious pathogen belonging to the Morbillivirus genus within the Paramyxoviridae family, known for causing a severe, rash-inducing illness. Despite an effective vaccine, MeV remains a global health concern, especially in regions with low vaccination coverage. Understanding the virus’s structure, cellular invasion, replication strategy, and immune evasion methods is central to controlling its spread. MeV is exceptionally efficient at transmission, with nearly 90% of exposed, non-immune individuals becoming infected.
Viral Architecture
The Measles Virus is an enveloped, roughly spherical particle, typically measuring between 100 and 250 nanometers in diameter. Its structure includes a lipid envelope derived from the host cell, which is studded with two functional spike glycoproteins. The Hemagglutinin (H) protein recognizes and binds to specific receptors on the host cell surface, initiating infection.
The Fusion (F) protein works with the H protein to facilitate the merging of the viral and host cell membranes. Beneath the envelope lies the Matrix (M) protein, which lines the inner surface of the membrane. The M protein connects the internal core to the external envelope and regulates the assembly of new viral particles.
Encased within the M protein layer is the nucleocapsid, a tightly coiled helical structure forming the core. This core contains the virus’s genetic blueprint: a single-stranded, non-segmented RNA molecule of negative polarity. The RNA genome is protected by thousands of copies of the Nucleoprotein (N), forming a ribonucleoprotein (RNP) complex. The RNP complex also includes the viral RNA-dependent RNA polymerase, composed of the Large (L) protein and its cofactor, the Phosphoprotein (P).
Cellular Invasion
Infection begins when the H protein recognizes and attaches to specific receptors on the host cell surface. This attachment determines the virus’s tropism, dictating which cells it can successfully invade. Measles Virus utilizes two main receptors: the Signaling Lymphocyte Activation Molecule (CD150), found predominantly on immune cells (T cells, B cells, macrophages, and dendritic cells), and Nectin-4 (PVRL4), an adherens junction protein found on epithelial cells.
Binding to CD150 allows the virus to initially infect immune cells in the respiratory tract, leading to dissemination throughout the lymphatic system. Following systemic replication, the virus targets the Nectin-4 receptor on the basal surface of airway epithelial cells. This final step allows the virus to be shed into respiratory droplets, enabling efficient transmission to a new host.
When the H protein binds to either receptor, it triggers a conformational change in the associated F protein. The F protein undergoes a structural rearrangement that exposes a fusion peptide, which inserts into the host cell membrane. This action forces the viral envelope and the host cell membrane to merge, a process known as membrane fusion. The fusion event releases the entire viral nucleocapsid, containing the negative-sense RNA genome and its polymerase complex, directly into the host cell’s cytoplasm.
Genome Copying and Assembly
As a negative-sense RNA virus, the MeV genome cannot be directly translated by the host cell. Upon entry, the viral RNA-dependent RNA polymerase (L and P proteins) immediately begins transcription. The polymerase uses the negative-sense genomic RNA as a template to synthesize multiple smaller, positive-sense messenger RNA (mRNA) molecules. Host ribosomes translate these mRNAs to produce the necessary viral proteins, including structural proteins (N, P, M, F, H, L) and non-structural proteins (C and V).
The polymerase complex must switch from generating short mRNA transcripts to synthesizing full-length copies of the viral genome, a process known as replication. This transition is regulated by the accumulation of newly synthesized N proteins. Once the N protein concentration reaches a threshold, the polymerase ignores the stop and start signals between genes on the RNA template. This results in the synthesis of a full-length, positive-sense RNA molecule, known as the antigenome, which is immediately encapsidated by the N protein.
The positive-sense antigenome then serves as a template for synthesizing new, full-length negative-sense genomes. These progeny genomes are tightly wrapped by the N protein as they are synthesized. The final stage is assembly, where the newly created nucleocapsids migrate toward the inner surface of the host cell membrane. They interact with the M protein, which has associated with the cytoplasmic tails of the H and F glycoproteins embedded in the membrane. This interaction drives the formation of the new virion, which buds out from the host cell, acquiring its lipid envelope and surface glycoproteins.
Subverting Host Defenses
The Measles Virus counteracts the host’s innate immune response primarily by interfering with the Type I Interferon (IFN) pathway. Interferons are signaling proteins released by infected cells to warn neighboring cells and initiate an antiviral state. The viral genome encodes two non-structural proteins, V and C, derived from the P gene, which are designed to silence this alarm.
The V and C proteins are potent immune antagonists that target the IFN signaling cascade. The V protein interferes with cellular sensors that detect viral RNA, preventing the activation of pathways leading to IFN production. The C protein also suppresses the host’s ability to produce Type I interferons, allowing the virus to replicate unchecked during initial infection.
MeV is particularly damaging because it causes profound and long-lasting immunosuppression, known as “immune amnesia.” Due to its tropism for CD150 receptors, the virus infects and destroys a large population of immune cells, including memory T cells and B cells. The depletion of these memory lymphocytes effectively erases the host’s pre-existing immunity to other diseases. This state of immune amnesia leads to increased vulnerability to secondary infections and can last for months or years following the acute infection.