WHY IS LYSSA THE DEADLIEST?

In the 1970s, Europe witnessed an unusual event as thousands of chicken heads descended from the sky, bringing joy and bewilderment to foxes and other wildlife. The reason behind this peculiar occurrence was a strategic effort to combat the relentless rabies epidemic that had plagued wildlife populations since the 1930s. Recognizing rabies as one of the deadliest viruses known to humanity, authorities sought innovative solutions. Lyssa can transform animals into enraged creatures and induce a zombie with a fear of water in humans. However, the intrigue surrounding Lyssa extends beyond the peculiar and lethal nature of its infection. What makes Lyssa truly captivating is its exceptional skill in evading our immune defenses. Viruses teeter on the boundary between life and death, essentially comprising a mere handful of genetic instructions reliant on living cells for replication. The lyssavirus, while straightforward for a virus, possesses a simplicity that underscores its effectiveness. With just five genes, encoding instructions for five crucial proteins, the lyssavirus adeptly tackles intricate challenges: infiltrating a mammal, evading its immune defenses, navigating to the brain, replicating itself, and propagating the infection to new hosts.

Let's explore the scenario of infection. It commences with a bite, often from a dog carrying myriad viruses in its saliva, penetrating deep into the tissue. The ultimate destination is your nerve cells, the neurons. These living electrochemical wires transmit signals throughout your body, stretching up to 1.5 meters, featuring cellular machinery on one end and a terminal on the other. The terminal is a communication hub between cells, where chemicals convey information. Lyssa likely attaches to crucial receptors involved in this process, infiltrating the unsuspecting nerve cells. Once inside, the virus faces a significant challenge. It must reach the cellular machinery to commandeer the cell and generate more viruses. Given the considerable length of neurons, this journey can extend quite a distance. A remedy lies within our cells: microtubules, providing structural support and a track system for Dynein motors—a remarkable delivery system fueled by energy. Comprising 50 proteins, ten times more than the virus, Dynein motors resemble tiny pairs of shoes. Lyssa cleverly employs one of its five proteins to exploit this system, directing it toward the nucleus. As for the immune response, it faces challenges. Infected civilian cells play a pivotal role in activating the immune system. However, in this scenario, the immune system's defensive actions are limited. When a virus attacks, the infected cells recognize the intrusion and release a multitude of interferons—a unique family of proteins. These interferons interfere with viral activities, yet their effectiveness may vary.

In a simplified explanation, Interferons act as alarms, signaling the immune system to produce antiviral defenses. Beyond that, they instruct normal cells to temporarily reduce protein production, hindering efficient virus replication. Interferons also induce cell transparency, a crucial aspect for immune cells to detect infections hidden within. To address this, the body employs MHC class I molecules as display windows into cell interiors. Cells routinely generate substances for survival, sampling these products and placing them in these miniature display windows, offering glimpses inside. Interferons play a role in amplifying this process, prompting cells to create an abundance of display windows, and enhancing transparency.

When a cell is infected, it typically displays virus parts in a window for immune cells to identify and instruct the infected cell to self-destruct, eliminating the trapped viruses. This method is highly effective in combating viral infections. However, Lyssa hinders the production of interferons by neurons, rendering itself nearly invisible to the immune system. Unlike many other viruses, Lyssa avoids killing its host during replication, preventing alarm systems from triggering. Instead, it discreetly moves from neuron to neuron, gradually advancing towards the brain. The duration of this phase varies, taking weeks to months, and occasionally even years, influenced by factors such as the bite location and the viral load in muscles. Lyssa exhibits remarkable patience until it reaches its ultimate destination: the brainstem. It is only at this point that the immune system detects the anomaly and responds. The immune system deploys Killer T Cells, its potent antivirus soldiers, to locate and eliminate infected cells, typically a pivotal moment in combating viral infections. However, in the case of rabies, this turns into a fatal paradox. Lyssa, with its unique set of 5 proteins, cunningly manipulates the immune system's brilliance. Given the delicate nature of the central nervous system, the immune system exercises extreme caution to avoid triggering potentially lethal responses in the brain. Access to the nervous system is restricted; immune cells must be invited and can be expelled. In a defensive measure, nerve cells can command T Cells to self-destruct if they perceive an overreaction. Lyssa exploits this vulnerability by inducing infected neurons to express the self-destruct order. Consequently, as the powerful defense cells arrive, they are compelled to commit suicide. This orchestrated destruction allows the virus to breach the brain stem, marking a point of no return and inevitably leading to the demise of the host.

The mystery surrounding Lyssavirus's lethality persists as its precise mechanism of causing death remains elusive. Unlike typical viruses that induce damage through rapid multiplication, cell destruction, and an ensuing immune response, Lyssa's impact is enigmatic. Brain tissue in rabies patients exhibits minimal, sometimes negligible, damage, challenging the conventional narrative of viral destruction. Current theories propose that Lyssa disrupts neuron communication within the brain, rendering it dysfunctional. This disruption leads to symptoms such as confusion, aggression, and paralysis. As the virus prepares to exit, it traverses neurons, moving away from the brain toward the salivary glands. The remarkable phenomenon of the virus reversing its course after traveling in one direction remains unexplained despite decades of research. Ultimately, Lyssa saturates saliva, setting the stage for transmission through mammalian bites, perpetuating the infectious cycle.

In what may resemble the onset of a zombie apocalypse, the transmission of rabies through human bites is not a known occurrence. However, as the end nears, the rapid development of encephalitis, a brain swelling accompanied by debilitating neurological symptoms, unfolds. From lethargy to paralysis, the progression is gradual, leading to the sudden failure of organs and eventual coma. Lyssa, the rabies virus, stands as one of the deadliest known viruses, with minimal survival rates once symptoms manifest. A glimmer of hope exists in the form of a vaccine—among the earliest developed by humans. The vaccine primes the immune system, ensuring a robust defense against Lyssa's tactics. Notably, the vaccine's efficacy extends even after exposure, crucial for individuals bitten by a potentially infected animal, like a bat. Given Lyssa's slow onset in the initial weeks, post-exposure vaccination remains a viable lifesaver. Rabies, an enduring menace throughout human history, underscores the importance of vaccination in confronting this ancient terror. Annually claiming the lives of approximately 60,000 individuals, with nearly half being children, this formidable adversary remains a persistent danger. Efforts toward complete eradication are distant, with the menacing presence concealed in shadows, forests, and diverse animal species. Its potential resurgence looms, poised to intensify if vigilance falters or if vaccine skepticism prevails. A collective aspiration resonates—a day when humanity conquers this peril, relegating it to the status of most mythical monster.