Bunyaviridae Molecular Biology

Genome Structure:

The genome of Bunyaviruses is divided into three segments, each wrapped in its own helical nucleocapsid. These three segments are named after their relative lengths, Large(L), Medium(M) and Small(S). The L segment codes for the RNA dependent RNA polymerase, the M segment codes for two envelope proteins, and the S segment codes for both the nucleocapsid and nonstructural protein. In order to assemble into an infectious virion, one of each of these three segments must be incorporated. Research suggests that frequently bunyaviruses may incorporate more than one segment of L,M or S into the virion without compromising transmissibility.

Ambisense:

Although almost all Bunyviruses are negative stranded RNA viruses, some viruses of the Phlebovirus genus demonstrate ambisense on the S segment of their genome. Ambisense means that the virus has coding regions on both the template and the complimentary strands. For example, a virus might produce RNA with genes in the pattern +,-,+ that can effectively be translated into two proteins. The complimentary RNA strand will look like -,+,- and can be translated into only one protein. Thus, both the template and the complimentary strands of RNA code for proteins.

Transcription:

Bunyaviridae researchers have not altogether defined the location of transcription of the viral genome once inside the cell. Studies have located the growing mRNA to the perinuclear region, and suggest a membrane-associated mode of transcription. The N protein, used primarily to form the nucleocapsid, is also necessary for transcription, as it interacts with the L protein (RNA dependent RNA polymerase) during transcription and also serves as an RNA chaperone. Cap stealing is used to prime transcription.

Interaction with the Immune System:

In response to infection with a Bunyavirus, human cells generate a protein called MxA that has been shown to impede viral replication. They also induce a type-1 interferon response that induces an antiviral state in nearby cells. To counteract this, some bunyaviruses such as RVFV generate IFN-antagonist proteins. These proteins reduce the transcription of mRNA coding for IFN.

Connection to the Clinical Presentation:

Some Bunyaviruses, especially Hantavirus, induce an outpouring of cytokines as a part of the host immune response to infection. In Hanta Pulmonary Syndrome, however, the amount of cytokines produced is so great that it damages the integrity of the host vascular system. This causes leakage of fluid from the capillaries resulting in pulmonary edema and potentially death.