Rabies Virus (RABV) Antibodies, Proteins & ELISA Kits

Rabies is caused by the negative sense, single-stranded RNA Rabies Virus (RABV), which belongs to the family Rhabdoviridae and the genus Lyssavirus. Rabies occurs worldwide but Asia and Africa accounts for 95% of the mortality rates. Rabies is mainly spread through the bite of a rabid animal or from an infected individual’s saliva.

RABV can infect any warm blooded animal and the main reservoirs for the virus are skunks, racoons, foxes, dogs and bats. The symptoms experienced by rabies infections include fever, weakness, headaches, hallucinations, insomnia and they can progress to paralysis and death. Following RABV infection an individual may receive post-exposure prophylaxis (PEP). PEP typically consists of wound washing, rabies immunoglobulin (RIG) administration and in some cases the administration of a rabies vaccine.

While there are currently vaccines approved for use in both animals and humans, there is the need for further research into the pathogenesis of RABV and the host immune response in order to continue the development and enhancement of rabies vaccines.

RABV has 6 proteins; a matrix protein (M), glycoprotein (G), nominal phosphoprotein (NS), phosphoprotein (P), nucleoprotein (N) and an RNA dependent protein (L). All of these antigens play a distinct role in mechanisms such as viral assembly, replication, host attachment, host cell entry and pathogenesis.

RABV binds to host receptors such as nicotinic acetylcholine receptor (nAChR), neuronal cell adhesion molecule (NCAM) and neurotrophin (NT) receptor, p75(NTR). It has been shown that when the G protein binds to nAChR, RABV accumulates at the neuromuscular junction and enhance it’s ability to be taken up by the nerve terminal.

Toll-like receptor 7 (TLR7) is involved in the induction of a humoral immune response during rabies infections. As well as this, infection with RABV activates the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome when the nucleotide-binding and oligomerization domain (NOD)-like receptor NLRP3 recognizes pathogen-associated molecular patterns (PAMPs) of the virus.

RABV has adapted numerous mechanisms for evading the host immune system during infections. For example, neurons that are infected with RABV have been shown to upregulate programmed cell death protein 1 (PD-1), HLA class I histocompatibility antigen, α chain G (HLA-G) and Fas ligand (FasL). The upregulation of these immune subversive molecules is known for triggering death signaling in activated T cells resulting in the killing of migratory T cells.

As well as this, RABV favors the survival of viral infected host neurons. A mechanism by which RABV inhibits apoptosis is through the sequestration of TLR3 into Negri bodies. RABV also tries to dampen the interferon (IFN) response during rabies infections.

It is important to get a better understanding of the host immune response to RABV in order to develop more efficacious vaccines against the virus. RABV is a neurotropic virus which enters the central nervous system (CNS) and there is the association of brain and spinal cord inflammation with rabies infections due to the immune response generated.

Some commonly observed cytokines which are produced during rabies infections are interleukin-6 (IL-6), IL-8, IL-10, IL-1beta, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IFN-alpha and IFN-beta. As well as this, MIP-1 alpha (CCL3), RANTES (CCL5) and IP-10 (CXCL10) chemokines are produced when RABV enters the body.

Immunometabolism is an important area of science which encompasses regions of metabolism and immunology. Many of the functional capacities of immune cells are dependent on the metabolic state of the cell and its capability to mount an immune response.

At present there is very little research covering how immune cell metabolism is affected by RABV, meaning it represents a potential research area for future investigations. Assay Genie provides a wide range of immunometabolism assays such as glycolysis, fatty acid oxidation, the citric acid (TCA) cycle and oxidative phosphorylation (OXPHOS) assays kits.

Animal models are useful research tools which are often used in early stages of therapeutic product development and pathogenesis studies. Since RABV infects any warm blooded animal, many different animal models can be used to model the disease for vaccine development. For example, mice are regularly used to model rabies infections and aid in vaccine studies. When mice are administered with virulent RABV, there is neuroinvasion observed and they die within 10-20 days of exposure. However, when attenuated RABV is administered, there is weight loss and neuroinvasion but the virus is rapidly cleared.