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College of Medicine Microbiology Medical Virology Viral infection and pathogenesis: Dr. Jawad Kadhim Tarrad -------------------------------------------------------------------------------------------Infection is presence and multiplication of pathogenic microbe within human body, and cause symptoms of infection. The infection differs from other diseases is that caused by living microbial pathogens. The disease is impairment of normal state of organism or any of its components that hinders the performance of vital functions. It is occurring due to malnutrition, physiologic disorder, inherent defect of body ,climate and industrial hazard, specific infectious agents, or combination of these. The disease term include infectious diseases and non-infectious diseases. The viral pathogenesis refers to ability of viruses to cause infections in human. Stages of viral infection: Transmission of virus from external source to host body through the portals of entry. Adhere to and /or invade susceptible host tissues. Multiply and spread to adjacent cells or to specific cells. Evasion of host defense mechanism. Damage the host tissues and disease symptoms. Progression or resolution of the disease. Shedding of virus in some instances. Main sources of infection: 1. Human: the common sources of infection are patients or carriers. The carrier is person recovered from disease but harboring virus in his body. Fomites are inanimate objects of patients that may be contaminated and serves as source of infection. 2. Animals: The infected animals can be serve either the source (reservoir) or made transmission (vector)of certain viruses as in arthropod-borne infection . 3. Food: the foods are most important media for transporting the viruses to human during consumption of contaminated food, and therefore act as food-borne infection. 1 4. Water: many viruses may be found in water. The infectious agents are transmitted to human by consumption of water or when swimming in it, therefore act as water-borne infection. Transmission and Portals of entry: Portals of entry(routes of infection) : Major: Minor: 1. Respiratory tract(nose). 1. Eye. 2. Elementary tract(mouth). 2. Anus. 3. Skin, non-intact. 3. Ear canal 4. Genital tract(vagina). 4. Urethral canal. Modes of transmission: Most viral infections are communicable capable of spreading from person to person. If a disease is highly communicable ,the term contagious is applied. The infectious agent is transmitted from source of infection to human either by vector (entity living such as insects, ticks and mite), or by vehicles (entity non-living such as fomites, water, food, air, medical devices and other inanimate objects). The infection is occurring or acquired from hospital, called hospitalacquired infection( nosocomial infection) . The infection obtained from outside the hospital among human community, called community-acquired infection. The subsequent infection by same organism in same patient is called re-infection. Horizontal transmission : Inhalation : the pathogenic agents may be transmitted by inhalation of respiratory secretions(air droplet nuclei containing infectious agents) of infected patients, or by inhalation of contaminated dust (air borne) with virus . Ingestion: the infectious agents can be transmitted by consumption (during eating or drinking) of contaminated water or food. Skin : any small break, abrasion, and wound in skin that permit initial entry. The transmission may occur through direct contact(such as handshaking, kissing)with infected person , infected animal or during handling of fomites of patients, or the organism is transmitted indirectly by vector bite . 2 Blood transfusion: some pathogenic microorganisms can be transmitted by blood transfusion. Injection of needles during intravenous drug use or indwelling catheter, have role in transmission. Sexual intercourse: certain pathogenic microorganisms can be transmitted by sexual contact in homosexual or heterosexual persons. Vertical transmission: The pathogen can transmit from infected mother to her fetus; across the placenta (prenatal) ,or at time of delivery from birth canal (perinatal), or during breast feeding(postnatal) . Adherence of virus to target cell: The viruses tend to exhibit cell and organ specificities (cell tropism ). The viral affinity for specific body tissue is dependent on : 1. Presence of specific cellular receptors on cell surface which interact with virus, and initial infection. 2. Ability of host cell to support viral replication such as Physical barriers, local temperature, pH, oxygen tension and nutrients are very important in tissue tropism. Invasion of host tissues(replication and dissemination): The viruses replicate and produce diseases at site of entry or at site distant from their point of entry. In other word, the viral infections are either localized on the portal of entry or spread systemically through the body. After primary replicate at site of entry , then the virus spread within body of the host from local replication to target cells . Mechanism of viral spread vary, the most common route is via blood stream, lymphatics or nerves. The presence of virus in blood stream is called viremia. Evasion of host defenses: The viruses when meet the host cell faced several antimicrobial defenses of host. The viruses have many mechanisms to avoid action of host defenses: Certain viruses encode some proteins act as receptors for immune mediators such as interferon (IFN) and tumor–necrosis factor (TNF). When the virus released from virus-infected cell , these proteins bind to immune mediators and block their ability to interact with receptor 3 on their intended target. Because reducing host defense, the virulence of virus is enhanced. These virus-encoded proteins that block host immune mediators are called cytokines decoys. Certain viruses have multiple antigenic types (multiple serotypes). The patient can be infected with one serotype , recover , and have antibodies that protect from infection by that serotype in future , however , that person can be infected by other serotypes of virus. Most viruses have one serotype , but certain have several serotypes such as rhinovirus which has more than 100 serotypes , this is the reason why the common cold by this virus is common. Antigenic variation may occur in certain viruses such influenza virus. Certain viruses are able to thwart immune defenses for numbers of reasons such as latent or can infect cell for long period without adverse effects on cell. Certain viruses are spread from cell to cell without exposed to immune system. They don’t form extracellular phase. Damage of host cell(pathogenesis) : The time between exposure to virus and onset of disease is called incubation period, it required to produce sufficient numbers of virus that lead to cause disease. This period reflects the time needed for the infectious agents to overcome early defense and grow to a population size. The mechanisms of viral diseases are various: 1. Most viral diseases are result in host cell death by several mechanisms: Shutoff macromolecules synthesis, or by Lyses of the cell membrane by lysozymes during viral replication, or by Induction of programmed cell death (suicide program, apoptosis) by some viruses (eg: HIV). 2. The pathogenesis may result from immunological attack: for example, The hepatitis viruses don’t cause a cytopathic effect in liver cells , but the damage of hepatocytes is result of recognition of viral antigens on hepatocyte surface by cytotoxic T-cell. Some viruses stimulate cellular cytokines that play important role in immunopathogenesis .For example, diarrhea caused by rotavirus, the rotavirus-infected cells produce cytokines that stimulate the enteric 4 neuron, resulting in excess fluid and electrolytes secretion into the bowel lumen. Damage caused by immune response of host to infection, the response is often which leading to harmful outcome for host such as hypersensitivity and autoimmune. Outcome of infection: If the host defenses overcome the virulent virus in first step, the disease is not occurring. If viral pathogens overcome the defenses of infected individual, the disease resulted and it may progress to cause death of infected host. If the host defenses overcome the virulent microbe after infection, this lead to repair and healing, and recovery from infection. If the host defense is failure to eliminate the microbe from the body, the infection may become chronic(persistent infection), which mean the microbes may continues to multiple and produce significant symptoms of disease for long period. Persistent viral infection: Three types of persistent viral infections: 1. Chronic infection: certain patients who have infected with some viruses continue to produce significant symptoms of disease and significant amount of virus for long period. 2. Latent infection: certain patients recover from initial infection and virus production stops. But the patients harboring the virus in their bodies (remain as carriers) without produce symptoms. 3. Slow virus infections: some infections require to long period between initial infection and onset of disease, which are usually measured in years (such as Kuru disease, and HIV). The mechanisms that may play a role in persistence of viral infections include: 1. Integration of provirus into chromosome of host cell without viral replication, as occur in retroviruses. 2. Spread from cell to cell without extracellular phase , so that is not exposed to immune response . 3. Occurrence of rapid antigenic variation in some viruses . 4. Location of virus within immunological sheltered e.g. : brain. 5 5. Immune tolerance may occur in some patients, because neutralizing antibodies are not formed. 6. Some patients suffer from immunosuppression , as in AIDS. Virus shedding: The last stage in pathogenesis is the shedding of infectious virus into environment. The shedding usually occurs from the body surface involved in viral entry. The shedding occurs at different stages of disease dependent on particular agent involved. Predisposing factors of infection: The infection does not arise in vacuum. It results from interaction of several factors. The risk factors that involved in the development of infections include mainly three factors: Microbial factors: virulent microbe should be having virulence factors (such as: adherence factors, invasive factors, factors mediating avoid host defenses and factors cause damage the tissue of infected host). Host factors: susceptible host is complaining from; defect or suppress in immune system, disorder in physiologic state and hormones, pregnancy, stress , malnutrition, age and race, and others. Environmental factors: Climate and seasonal variations, activities of some microbes and vectors are increased. Lifestyle, social and behavior changes, economic and hygiene status, foreign bodies (indwelling devices), housing and crowding, all these facilitate infection. 6