Adenovirus Pathogenocity And Immunity Biology Essay

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Pathogenocity- The ability of an infectious agent to cause a diseased state in an organism as a result of a genetic component in a pathogen and the overt damage done to the host due to its interaction with the pathogen is known as Pathogenocity.

Pathogenocity is often explained in terms of Virulence. Virulence is the degree of pathology caused by an infectious agent. Adenovirus is known to primarily infect the epithelial tissues in the upper respiratory tract and the enteric organs. The adenovirus can gain entry into the host through the eye, nose, mouth and sometimes via skin. Adenovirus is ubiquitous in nature. Children less than 5 years are more vulnerable because of their relatively low levels of immune surveillance. An important fact to be noted in an Ad infection is that the virus is continually shed in faeces even months after the first infections. [1] Even though the host no longer seems to have any symptoms of the infection, the virus tends to remain inside the host and exhibits latency.

Factors involved in the Pathogenicity

There are a number of factors that play a crucial role in the pathogenicity of the adenovirus inside a host like the virus ability to enter a host, to survive & grow in them, to combat host defense mechanism and to inflict temporary/permanent damage to the host cell by the process of cell lysis, inducing toxins, transformation of the cell or structural alterations of the cell (Cytopathic effect).

Once the adenovirus enters the host cell and gauges the available environment it produces the desired raw materials necessary for it to survive and replicate (some of which are proteins specific to evade the immune cells). Some of the adenoviral proteins known to assist in avoiding the host cell immune action such as apoptosis originate from the E3 transcription unit. E3gp19K protein encoded by the E3 region acts as the first line of defense against the Cytotoxic T cells. This is specific only to the adenoviruses infecting the respiratory tract and other adenovirus infections. E3 is referred to as the Stealth gene. [2] Other E3 encoded protein E3-14.7kDa (Adenovirus Death Protein) plays a role in the release of newly synthesized virions from an infected cell. [3] The immune system of the host sets up an alarm when the cell’s normal functions are disrupted. This triggers apoptosis leading to the killing of an infected cell. The adenovirus however, has it’s own set up to counter the host defense action. This is taken care of an early protein called E1B55k, which shuts down the apoptosis initiating pathway. The adenovirus deals with this problem by expressing a protein called E1B55k protein that plays a role in shutting down the system, leading to the activation of the apoptosis. This gives the adenovirus ample time to multiply and cause a diseased state. Adenovirus avoids the T cell activity by retaining the MHC I within the Endoplasmic Reticulum. In order to make a congenial environment for the viral genome replication to occur they alter the intracellular environment and have adverse effects on host cellular functions. This degenerative change in the host cell machinery due to the viral replication is referred to as Cytopathic Effect. Typically, in an adenovirus infection the cytopathogenic effect (CPE) is defined by a rounding and grapelike clustering of the infected cells. [4] Initial CPE may start at the periphery of the monolayer before generalizing. However, not all species of adenovirus causes enlargement or clustering of the infected cell. In a HeLa cell culture, the cytopathic effects are more clearly noted- early clumping of the cells due to protein products and nuclear alterations caused by the virus itself. The adenovirus speeds up the glycolysis step to increase the quantity of the acids which changes colors due to change in the pH levels. This helps in examining the CPE changes. [5]

SYMPTOMS

The symptoms caused due to an adenovirus infection, includes, cold, sore throat, bronchitis, pneumonia, diarrhea, conjunctivitis, gastroenteritis and in some rare cases Hepatitis. Usually an adenovirus infection is limited to immunocompromised host. They have the ability to cause severe necrotizing pneumonia, where a part or the entire lung is translucent radiographically. This condition is referred to as Swyer-James syndrome. It also causes the lung to shrink in volume and increase the respiratory related illness.

IMMUNE ACTION

The cell mediated immunity forms the immunologic defense against the adenovirus infection. It was observed that infections occur primarily in host whose cellular immunity is compromised. Several experimentations on Rodents seems to indicate that cellular immunity is mandatory to protect a host from Ad infection. Cell mediated immunity is of two types-specific (MHC class I and II) and non-specific. Macrophages and NK cells are a part of the non-specific category of the cell-mediated immunity. NK cells play a crucial immunomodulatroy role in the cell-mediated immunity. It does not require the expression of class I or II. The killing of a foreign pathogen by the NK cells can be augmented by release of cytokines such as IL-1 and IL-2. Lymphocyteâ€"activated Killer cells originate from NK cells activate the various cytokines and Interferon and mediate a non-MHC cytotoxicity that kills the foreign pathogen. [6]

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