Hantaviruses are members of the Hantaviridae family, enveloped viruses that carry their genetic information as single-stranded RNA. They are recognized for causing diseases in humans. The architecture of the hantavirus particle, or virion, provides the tools it needs to enter a host cell, replicate its genetic material, and spread.
The Viral Envelope and Surface Proteins
The exterior of a hantavirus virion is a lipid envelope, which gives the particle a generally spherical, though sometimes oval or varied (pleomorphic), shape. This outer membrane is acquired from the host cell during the final stages of viral assembly. The diameter of these viral particles can range from approximately 70 to 350 nanometers. This host-derived envelope provides a protective barrier for the internal viral components.
Embedded within this lipid bilayer are glycoproteins that appear as spikes on the viral surface, extending about 10 nanometers. These spikes are composed of two proteins, Gn and Gc, organized into specific arrangements. The Gn protein forms the stalk of the spike, while the Gc protein forms the head.
The Gn and Gc glycoproteins initiate infection by binding to specific receptor molecules, such as integrins, on the surface of host cells. This attachment is the first step in the viral life cycle. Following attachment, these glycoproteins facilitate the fusion of the viral envelope with the host cell’s membrane. This action delivers the internal viral contents into the cell’s cytoplasm.
The Internal Nucleocapsid
Once inside the protective envelope, the hantavirus’s genetic material is not found freely floating. Instead, it is securely packaged by a structural protein called the nucleocapsid (N) protein. This protein binds tightly to the viral RNA, forming ribonucleoprotein (RNP) complexes. This packaging is a defense mechanism, shielding the fragile RNA genome from cellular enzymes that could otherwise degrade it.
Each of the three genome segments forms its own RNP complex with the N protein. These RNPs are coiled into a helical shape. The ends of the RNA segments are held together by non-covalent bonds, giving the RNP a circular appearance, a conformation that is active in the viral life cycle.
The N protein is one of the most abundant proteins produced during an infection. Its primary function is to condense and protect the genome within the virion. The RNP structure is also directly involved in viral replication and transcription, helping regulate how the genetic code is read and copied inside a host cell.
The Segmented RNA Genome
A hantavirus’s genetic material is a single-stranded, negative-sense RNA genome. This genome is segmented into three pieces of varying sizes: Small (S), Medium (M), and Large (L). This strategy is common in the Bunyavirales order, and each segment contains instructions for producing specific viral proteins.
The S segment of the genome encodes the nucleocapsid (N) protein. The abundant production of the N protein is necessary to package newly synthesized copies of the viral genome during replication. In some hantaviruses, the S segment also contains the code for a non-structural protein (NSs) that helps the virus evade the host’s immune response.
The M segment carries the genetic code for a glycoprotein precursor (GPC). After this precursor is produced, it is cut by cellular enzymes into the two surface glycoproteins, Gn and Gc. These are the proteins that form the spikes on the viral envelope responsible for cell entry.
Finally, the L segment is the largest of the three and encodes the L protein. This protein is an enzyme known as an RNA-dependent RNA polymerase (RdRp). The L protein is the machinery that reads the virus’s negative-sense RNA to create new copies of the genome and to transcribe messenger RNA (mRNA). A copy of the L protein is attached to each RNP complex inside the virion.
Structural Role in Viral Replication
The structural components of the hantavirus work in a coordinated fashion to replicate the virus. Replication begins when the Gn and Gc glycoproteins on the viral envelope attach to receptors on a host cell’s surface. This interaction is highly specific and determines which cells the virus can infect.
Following attachment, the viral envelope fuses with a host cell membrane, releasing the three RNP complexes into the cytoplasm. Once free, the L protein begins transcribing the viral RNA into messenger RNA (mRNA). The host cell’s ribosomes then translate the mRNA to produce new viral proteins.
New viral proteins and replicated RNA segments assemble at the Golgi apparatus. The N protein packages the new genomes into RNPs, while the Gn and Gc glycoproteins insert into the Golgi membrane. The RNPs then associate with these membranes and bud into the Golgi, acquiring their lipid envelope to form complete virions ready to exit the cell.