Measles Virus: Structure, Entry, Replication, and Immune Evasion

Measles, a highly contagious viral disease, remains a significant public health concern worldwide. Despite the availability of an effective vaccine, outbreaks continue to occur, highlighting the virus’s persistence. Understanding the biology of the measles virus is essential for developing better prevention and treatment strategies.

This article explores various aspects of the measles virus, including its structure, how it enters host cells, its replication process, mechanisms of immune evasion, and how it spreads from cell to cell.

Measles Virus Structure

The measles virus, a member of the Paramyxoviridae family, has a structural composition that contributes to its infectious capabilities. The virus is enveloped, possessing a lipid membrane derived from the host cell during viral budding. This envelope contains two glycoproteins: the hemagglutinin (H) protein and the fusion (F) protein. The H protein binds to host cell receptors, initiating infection, while the F protein facilitates the fusion of the viral envelope with the host cell membrane, allowing the viral genome to enter the host cell.

Beneath the envelope is the matrix (M) protein, which provides structural integrity and plays a role in virus assembly and budding. The viral genome is a single-stranded, negative-sense RNA, encapsulated by the nucleocapsid (N) protein. This RNA genome encodes several proteins, including the polymerase complex, essential for viral replication. The N protein, along with the phosphoprotein (P) and large protein (L), forms the ribonucleoprotein complex, crucial for the transcription and replication of the viral genome.

Host Cell Entry

The interaction between the measles virus and its host begins with molecular recognition and binding. The virus encounters the host cell with its hemagglutinin (H) protein seeking specific cellular receptors, primarily the signaling lymphocyte activation molecule (SLAM) and nectin-4. Once the H protein binds to these receptors, a conformational change occurs, setting the stage for the next phase of entry.

This binding activates the fusion (F) protein, facilitating the merging of the viral envelope with the host cell membrane. The F protein undergoes a structural transformation, allowing it to insert into the host cell membrane. This insertion brings the viral and cellular membranes into proximity, resulting in their fusion and the release of the viral ribonucleoprotein complex into the host cytoplasm. This fusion process exemplifies the virus’s adaptations to maximize entry efficiency.

Once inside the host cell, the viral components initiate the replication cycle. The entry of the viral genome into the cytoplasm marks the beginning of a complex interplay between viral and host factors. The virus exploits host machinery to support its replication and transcription, hijacking cellular resources to propagate the infectious cycle further.

Replication Process

Once the measles virus enters the host cell, the replication process begins with the viral ribonucleoprotein complex. This complex, comprising the RNA genome tightly associated with viral proteins, serves as the template for both transcription and replication. The first task is to transcribe the negative-sense RNA into positive-sense mRNA, a process mediated by the viral RNA-dependent RNA polymerase. This enzyme, composed of the phosphoprotein and the large protein, orchestrates the synthesis of viral mRNAs, which are subsequently translated into viral proteins by the host’s ribosomal machinery.

As viral proteins accumulate within the host cell, they facilitate the replication of the viral genome. The nucleocapsid protein encapsidates newly synthesized RNA, ensuring its stability and functionality. Meanwhile, the matrix protein aids in organizing viral components for efficient assembly. The replication of the genome involves synthesizing a full-length positive-sense RNA intermediate, which then serves as the template for generating new negative-sense RNA genomes.

The coordinated synthesis of viral components leads to the assembly of new virions. These newly formed viral particles congregate at the host cell membrane, where budding occurs. During this process, the matrix protein plays a role in driving the budding of the virus by interacting with both the nucleocapsid and the cellular membrane. This culminates in the release of infectious virions into the extracellular environment, ready to infect neighboring cells.

Immune Evasion

The measles virus has evolved strategies to circumvent the host’s immune defenses, ensuring its survival and propagation. One tactic is the suppression of the host’s interferon response, a component of the innate immune system. By disrupting the signaling pathways that activate interferon production, the virus diminishes the host’s initial antiviral response, allowing it to establish infection more effectively.

The virus also modulates the function of dendritic cells, which are pivotal in presenting antigens to T cells, a process crucial for mounting an adaptive immune response. The measles virus impairs dendritic cell maturation and function, hindering the activation of T cells and delaying the adaptive immune response. This interference prolongs viral persistence and facilitates the virus’s spread within the host.

Cell-to-Cell Spread Mechanism

The measles virus can move from one cell to another, spreading the infection while largely evading extracellular immune detection. This cell-to-cell transmission is facilitated by the virus’s ability to induce the formation of syncytia, which are large, multinucleated cells formed by the fusion of infected cells with neighboring uninfected ones. This fusion process is mediated by the viral fusion protein, which remains active on the surface of infected cells, enabling direct contact and subsequent fusion with adjacent cells.

Syncytia formation allows the virus to disseminate within tissues without exposing itself to antibodies circulating in the bloodstream. This mechanism is effective in tissues such as the respiratory tract and lymphoid organs, where the virus can quickly spread to a large number of cells. By circumventing the extracellular environment, the measles virus minimizes its exposure to neutralizing antibodies, which could otherwise limit its propagation. This mode of spread highlights the virus’s adaptations to thrive within its host while minimizing immune detection.