Viral Infection: Effects and Inclusion Bodies

Effects of Viral Infection on Cells

• Viruses can induce cell death, as seen with herpes and enteroviruses.
• Inclusion bodies, abnormal structures composed of viral proteins or genetic material, may form within infected cells.
• Viruses like respiratory syncytial virus (RSV) can cause cell membranes to fuse, leading to syncytia.
• Cytopathic effects refer to morphological or functional changes in cells due to viral infection.
• Management transformation occurs when viruses, like human papillomavirus (HPV), cause cells to become cancerous.
• Some viral infections do not result in apparent morphological or functional changes in the host cell.

What Are Inclusion Bodies?

• Inclusion bodies are abnormal structures formed within a cell during viral infection, composed of viral proteins, RNA, DNA, and sometimes host cell components.
• They indicate active viral replication, disrupt normal cellular functions, aid in immune evasion, serve as diagnostic markers, and alter cellular signaling.
• Intracytoplasmic inclusion bodies are found in the cytoplasm; Negri bodies, formed by the rabies virus, exemplifies this type.
• Intranuclear inclusion bodies are located in the nucleus, a characteristic seen in herpesvirus infections.
• Inclusion bodies are sites where viral components concentrate, facilitating virion assembly.
• Their formation can disrupt normal cell processes, leading to cell damage, dysfunction, or death, causing viral infection symptoms.
• Some viruses use inclusion bodies to conceal viral proteins or genetic material from immune cells, evading detection until a high viral load is achieved
• The presence of inclusion bodies, such as Negri bodies in brain tissue, can confirm a rabies infection.
• Inclusion bodies can alter cellular communication, prioritizing viral replication over normal cell processes and affecting cell survival.

Fusion of Cells to Form Multinucleated Cells

• Viruses like RSV, herpesvirus, and measles virus can cause cell fusion, resulting in syncytia.
• Viral surface glycoproteins, such as the F protein in RSV, facilitate the merging of the virus envelope with the host cell membrane.
• After viral entry, viral proteins interact with adjacent cells' membranes, causing them to fuse.
• Syncytia formation allows efficient viral replication via housing particles and utilizing all the necessary cellular machinery.

Importance of Cell Fusion for Viral Infection

• Syncytia help viruses evade immune detection by reducing viral particles on the cell surface.
• Fusion creates an efficient environment for viral replication, boosting viral loads and accelerating infection spread.
• Syncytia enable direct cell-to-cell viral transmission, a faster method than relying on free viral particles.
• Direct cell-to-cell transmission helps viruses avoid extracellular spaces where immune cells could detect and destroy them.
• Syncytia formation contributes to tissue damage by causing infected cells to malfunction and die, resulting in inflammation and cell death.

Clinical Relevance of Cell Fusion

• RSV induces syncytia in lung cells, causing severe respiratory issues like bronchiolitis and pneumonia.
• Some herpesviruses lead to multinucleated giant cells.
• The measles virus induces cell fusion, leading to giant cells.
• Cell fusion facilitates viral replication and promotes transmission between cells.

How the Immune System Responds to Viruses

• Viruses invade living cells to replicate, attaching to host cells via surface proteins or glycoproteins.
• After entering a cell, the virus turns it into a virus factory, replicating and spreading to nearby cells.
• The innate immune system, an immediate response, involves interferons, natural killer cells, and antigen-presenting cells.
• Interferons are signaling proteins that warn neighboring cells of viral infection.
• They bind to receptors on uninfected cells, triggering the production of antiviral proteins that prevent viral replication.
• Interferons induce nearby cells to increase the expression of MHC class I molecules, which present antigens to immune cells.
• MHC class I molecules present antigens to adaptive and innate immune cells.
• Natural killer (NK) cells recognize antigens on MHC class I molecules and kill infected cells.
• NK cells release toxic substances like granzymes and perforin to kill virus-infected cells lacking MHC class I molecules.
• Macrophages ingest free viruses through phagocytosis and present antigens to trigger immune responses.
• Dendritic cells bridge the innate and adaptive immune responses by capturing, processing, and presenting antigens.
• The adaptive immune system involves T cells, B cells, and antibodies.
• Viral fragments presented on MHC class I molecules attract cytotoxic T cells.
• Cytotoxic T cells (CD8+ T cells) kill infected cells by releasing cytotoxic factors, inducing cell lysis or apoptosis.
• Macrophages engulf and remove dead cells.

B Cell Response

• B cells produce antibodies that target viral antigens.
• Before antibody production, B and T cells interact through a series of steps.
• The B cell receptor recognizes the viral antigen, internalizes it, and presents it on MHC class II molecules.
• CD4+ T cells (T helper cells) interact with viral antigens presented by dendritic cells.
• The process primes CD4+ T cells, stimulating their maturation.
• The activated B cell gives rise to long-lasting memory B cells and antibody-secreting plasma cells.

Immunological Memory

• Memory cells, including memory B and T cells, ensure a swift response upon subsequent exposure to a specific virus, forming the basis for vaccines.
• Plasma cells secrete antibodies specific to the viral antigen encountered.
• Antibodies neutralize free virus particles, preventing them from infecting host cells.
• Antibodies mark free viruses for phagocytosis through opsonization.
• Antibodies activate the complement system, leading to the formation of the membrane attack complex (MAC), which lyses infected cells.
• Antibodies bind to infected cells, activating NK cells, which release cytotoxic factors to kill the target cells in a process called antibody-dependent cell-mediated cytotoxicity (ADCC).

How Antibodies Fight Viruses

• Neutralization: Blocking viruses from infecting cells.
• Opsonization: Marking viruses for phagocytosis by immune cells.
• Complement Activation: Triggering the complement system, leading to the destruction of infected cells.
• ADCC: Binding to infected cells and signaling NK cells to destroy them.

Host Defenses and Immune Response

• Interferons, natural killer cells, and macrophages define the innate immune response.
• T cells, B cells, and antibodies define the adaptive immune response.
• Memory cells facilitate long-lasting immunity after initial virus exposure, which is the basis for vaccines.