Lecture 7 - Viral-Host Interaction.pdf

Lecture 7: Viral Pathogenesis Viral Pathogenesis How a virus causes a disease Disease symptoms can result in tissue damage Can be caused by virus or the host immune response Terminologies Viral disease is some harmful abnormality that results from viral infection of the host organism Clinical diseas...

Lecture 7: Viral Pathogenesis Viral Pathogenesis How a virus causes a disease Disease symptoms can result in tissue damage Can be caused by virus or the host immune response Terminologies Viral disease is some harmful abnormality that results from viral infection of the host organism Clinical disease in a host consists of overt signs and symptoms. A virus is pathogenic for a particular host if it can infect and cause signs of disease in that host. A strain of a certain virus is more virulent than another strain if it commonly produces more severe disease in a susceptible host. Viral virulence in intact animals should not be confused with cytopathogenicity for cultured cells. Viruses highly cytocidal in vitro may be harmless in vivo, and, conversely, noncytocidal viruses may cause severe disease. Viral Pathogenesis Steps in Viral Pathogenesis 1. Entry and primary replication 2. Viral spread 3. Cellular injury 4. Host immune response 5. Viral clearance or establishment of persistent infection 6. Viral shedding 1. Entry and Primary Infection For host infection to occur, a virus must first attach to and enter cells of one of the body surfaces—skin, respiratory tract, gastrointestinal tract, urogenital tract A. Respiratory Tract Two parts: 1. Upper respiratory tract (URT) - The epithelium contains abundant goblet cells that produce mucus, a thick fluid that traps inhaled particulate matter. - Majority is lined with cilia, small hairlike structures that move together like oars to push the mucus and its trapped contents to the throat, where it is swallowed. 2. Lower respiratory tract (LRT) - Within the lungs, the two bronchi branch into bronchioles that lead to an estimated 300 million alveoli where gas exchange occurs - Smaller aerosolized particles or liquids are able to travel into the lower respiratory tract (larger droplets are deposited in the URT). - Mucus-secreting goblet cells are less abundant. - Ciliated cells are present at the beginning of the lower respiratory tract but are absent in the alveoli of the lungs. - Within the alveoli of the lung are found many alveolar macrophages A. Respiratory Tract A. Respiratory Tract - Most common portal of entry for viruses into the human body The mucosal surfaces of the respiratory tract translate to a very large surface area with which viruses can interact. * - A resting human inhales around 2 gallons of air every minute, and within each breath are aerosolized droplets and particles that could contain viruses, such as from a cough or sneeze of an infected individual. B. Gastrointestinal Tract - A hollow tube that stretches from the oral cavity (mouth) to the anus. - The small intestine is composed of fingerlike projections called villi that increase the surface area of the epithelium. - Under the epithelium of the small intestine, lymph node–like masses called Peyer’s patches contain millions of antibody - secreting lymphocytes, macrophages, and other immune system cells. - Interspersed within the epithelial layer are M (microfold) cells, specialized epithelial cells that constantly survey the contents of the small intestine lumen. These cells transfer the molecules from the lumen to the immune system cells found in the lymphoid tissue below (Peyer’s patch). B. Gastrointestinal Tract Viruses that enter via the gastrointestinal tract must be able to survive its hostile environment*. Successful viruses must be resistant to the low pH and the detergent qualities of bile The membrane envelopes of most enveloped viruses are disintegrated by bile. Acid-labile viruses (viruses that are easily destroyed in acidic environment) are unable to withstand the low pH of the stomach, while acid-resistant viruses contain capsid proteins that are not denatured by low pH (or their protein denaturation is reversible). Within the Picornaviridae family, rhinoviruses are acid labile, whereas poliovirus is acid resistant. Poliovirus, reovirus, and HIV are thought to exploit M cells to gain entry past the epithelium Poliovirus: Dissemination pathway for poliovirus in human. Oral ingested PV invades into blood through gastrointestinal tract followed by viremia (viruses entering the bloodstream). The virus in the blood permeates the blood brain barrier (BBB) into CNS (B). PV also invades into CNS directly by neural pathway through MNs from skeletal muscle to CNS (C). C. Urogenital Tract The genital tract refers to the organs that are involved in reproduction. Viruses that are transmitted via the genital tract as a result of sexual activity are sexually transmitted diseases. Cells can be infected, exhibited by the tropism of human papillomavirus (HPV) for the epithelium of the cervix or penis, or viruses can gain entry into the body through breaks in the genital epithelium or by binding local cell receptors, as occurs with hepatitis B virus (HBV) or human immunodeficiency virus (HIV). D. Skin Composed of two layers of tissue: the outermost epidermis and the underlying dermis Viruses that replicate in the epidermis, such as HPV, gain access through small cuts or abrasions in the skin that allow access to the lower, dividing layers of skin where viral replication can occur Bites of insect vectors (mosquitoes, ticks, mites) can introduce viruses into the dermis, and the subcutaneous tissue can be accessed by viruses through animal bites, needle punctures, or improperly sterilized tattooing or piercing equipment. E. Placenta Congenital Infections: - occur when a mother infects a fetus before its birth - occur via vertical transmission (generational transmission of viruses from parents to their offspring) - Vertical transmission often leads to long-term persistence of the virus within the child. - can occur when a virus crosses the placenta during pregnancy. The blood of the mother is not mixed with the blood of the fetus; instead, the placenta is the interface between the mother and developing fetus, allowing oxygen, waste products, and nutrients to pass between mother and fetus (see image). - Transplacental Infection vs Perinatal Infection 2. Viral Spread Tropism determines the pattern of systemic illness produced during a viral infection. Ex. hepatitis B virus has a tropism for hepatocytes, where disease is caused by the virus. There are 4 factors that affect Viral Tropism* Many viruses produce disease at sites distant from their point of entry. After primary replication at the site of entry, these viruses then disseminate within the host Mechanisms of viral spread vary, but the most common route is via the bloodstream or lymphatics. The presence of virus in the blood is called viremia. Virions may be free in the plasma (eg, enteroviruses, togaviruses) or associated with particular cell types. Characteristics of Viremia Neural Spread Directional Release to the outer surface allow evasion of the immune response* Sinusoids/ Fenestrations with immune cells Trojan Horse Approach (Diapedesis) 3. Cell Injury and Clinical Illness Destruction of virus-infected cells in the target tissues and physiological immune response of the host contribute to the disease development Clinical illness is an insensitive indicator of viral infection; but inapparent infections by viruses are very common. Lytic vs Lysogenic response 4-5. Host Defense/ Recovery from Infection Innate (nonspecific) immune response Physical barriers (e.g. tight junctions in the skin, epithelial and mucous membrane surfaces, mucus itself) Anatomical barriers (e.g. eyes- tears; skinsweat, desquamation, flushing; blood-brain barrier, gastrointestinal tract- gut flora, digestive enzymes) Epithelial and phagocytic enzymes (e.g. lysozymes) Phagocytes (neutrophils, monocytes, macrophages) Inflammation-related serum proteins - Cells that release cytokines and inflammatory mediators (i.e., macrophages, mast cells, natural-killer cells) Adaptive immune response (acquired/specific) Carried out by lymphocytes (B cells, T cells) two types of immunity humoral immunity: B cells differentiate into plasma B cells that can produce antibodies against a specific antigen. cell-mediated immunity: primarily directed at intracellular infectious agents Discuss Further 6. Viral Shedding pertains to the shedding of infectious virus into the environment last stage in viral pathogenesis Shedding usually occurs from the body surfaces involved in viral entry and occurs at different stages of disease depending on the particular agent involved. It represents the time at which an infected individual is infectious to contacts. In some viral infections, such as rabies, humans represent dead-end infections, and shedding does not occur. How does the environment affect viral transmission? 6. Viral Shedding Modes of Transmission A. Direct transmission: - transfer of the virus by direct contact or droplet spread - direct contact: may include skin-to-skin contact, sexual intercourse, or kissing droplet spread: includes the transmission of virions in respiratory droplets that are sneezed or coughed out of one person and immediately enter the respiratory tract of another person B. Indirect transmission: - requires the presence of an intermediary between hosts - airborne transmission: carried by dust or aerosolized particles that remain suspended in the air for long periods of time - fomites: nonliving physical substances that can indirectly transmit virions - Transmission via vectors - living intermediaries that can also transmit viruses (e.g. mosquitoes, ticks). Since these are arthropods, the terms arbovirus is used to denote arthropod-borne viruses. References