Background
Rabies virus (RABV) is a highly lethal neurotropic virus belonging to the Lyssavirus genus of the Rhabdoviridae family. Rabies, caused by RABV, is a disease that infects the nervous system of animals or humans, ultimately leading to fatal encephalitis. The primary mode of transmission is through the bite of an infected animal, particularly dogs, whose saliva carries the virus and transmits it to other animals or humans. Rabies is a serious public health issue; although it is preventable with vaccines, tens of thousands of people die from rabies each year, especially in densely populated regions where canine rabies is not effectively controlled. The rabies virus has a characteristic bullet-shaped structure, about 180 nm in length and 75 nm in diameter at its cross-section. One end of the virus is rounded or conical, while the other end is flat or concave. This unique morphology is an important identifying feature when observed under a microscope. RABV's genome consists of a single-stranded negative-sense RNA of nearly 12,000 nucleotides, encoding five viral proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and RNA-dependent RNA polymerase (L). These viral proteins not only determine the structure and function of the virus but are also closely associated with its pathogenicity. The rabies virus is enveloped, with approximately 400 glycoprotein trimers distributed over the surface of the viral envelope. These glycoprotein spikes help the virus bind to host cell receptors. The virus primarily attaches to the host cells through interactions with nicotinic acetylcholine receptors (nAChR), as well as other receptors like neural cell adhesion molecule (NCAM) and p75 neurotrophin receptor (p75NTR). After binding to these receptors, the virus enters the host cell through endocytosis. Once inside, the viral envelope fuses with the host's endosomal membrane, releasing the viral genome into the cytoplasm, initiating the replication and transcription process.
The length of time that rabies takes to incubate depends on where the bite occurred and how far away the brain was. The virus causes widespread neuronal infection and eventually deadly encephalitis after entering the central nervous system (CNS) through retrograde axonal transport. The virus becomes broadly dispersed throughout the central nervous system during this process as it travels through synapses from one neuron to another. This special mode of transmission enables the virus to avoid the host's immune system while sustaining little cellular harm, progressively impairing the host's neurological system. Fever, headache, and tingling at the injection site are early signs of rabies. Patients may develop hydrophobia, severe agitation, disorientation, and muscle paralysis as the illness worsens. Rabies usually kills the victim once neurological signs start to show. Despite having a death rate of over 100%, rabies can be avoided with vaccination. Rabies can be avoided with the help of post-exposure prophylaxis (PEP) and vaccinations given soon after exposure. The life cycle of the rabies virus is rather intricate. The viral genome is released once it has entered the host cell, and the negative-sense RNA is converted into mRNA, which is subsequently translated into the five viral proteins. In the late stages of infection, the viral polymerase shifts to RNA replication, generating more viral genomes. These newly synthesized RNA molecules combine with nucleoprotein (N) to form ribonucleoprotein (RNP) complexes. Subsequently, other viral components, such as matrix protein and glycoprotein, assemble into new viral particles, which eventually bud from the host cell membrane, completing the formation and release of new viruses, ready to infect other cells. RABV's high pathogenicity is closely related to its sophisticated immune evasion mechanisms. Research shows that the rabies virus can suppress the host's interferon (IFN) signaling pathway through its phosphoprotein (P), weakening the host's immune response. Interferon is a crucial defense mechanism in the host's response to viral infections, and RABV's ability to disrupt this pathway is one of the key reasons for its lethal nature when infecting a host. Rabies affects not only humans but also many mammalian species, particularly dogs, cats, and bats. In fact, in many regions with high rabies incidence, dogs are the primary source of human rabies infections. Bat-associated rabies viruses are also becoming more prominent, especially in the Americas, where bats are the main host responsible for rabies cases. As human activities expand and natural habitats are disrupted, human-bat interactions increase, raising the risk of rabies virus transmission from bats.
Figure 1. Various interactions between RABV proteins and the IFN signaling pathway (Source: Zhang H,et al., 2022)
The development and application of rabies vaccines are key strategies in controlling the spread of rabies. Since Louis Pasteur first developed a rabies vaccine in 1885, significant progress has been made in rabies prevention and control. Rabies vaccines are now used both for post-exposure treatment and for prophylactic vaccination in high-risk populations, particularly in regions with a high incidence of rabies and among individuals at occupational risk (such as veterinarians and field workers). Additionally, vaccinating animals, especially dogs, is crucial for preventing the spread of rabies to humans. Large-scale dog vaccination programs can significantly reduce canine rabies transmission, subsequently decreasing human rabies cases. Although rabies remains a serious global public health problem, it is a disease that can be fully controlled and eventually eradicated through enhanced surveillance, expanded vaccination coverage, and increased public health education. In densely populated areas, strengthening pet, particularly canine, vaccination programs and administering timely PEP treatment to potential exposure victims can significantly reduce rabies transmission and mortality rates. As a highly fatal neurotropic virus, RABV research is essential for understanding its neuroinvasive mechanisms, developing antiviral therapies, and exploring immune responses in the nervous system.
Alternative Names
Rabies IgG ELISA kit
Anti-rabies virus antibody detection kit
Rabies virus IgG antibody ELISA
References
- 1. Zhang H, et al. Regulation of innate immune responses by rabies virus. Anim Models Exp Med. 2022;5:418-429.