unit 12 review
Viruses are fascinating microorganisms that blur the line between living and non-living entities. They rely on host cells to replicate, causing a wide range of diseases in humans, animals, and plants. Understanding viral structure, replication, and host interactions is crucial for developing effective treatments and prevention strategies.
This unit explores viral pathogenesis and disease mechanisms, covering topics from viral entry and replication to immune responses and evasion strategies. We'll examine how viruses interact with host cells, cause disease, and spread within populations, as well as current approaches to treatment and prevention.
Viral Structure and Classification
- Viruses are non-living infectious agents that require host cells to replicate
- Consist of genetic material (DNA or RNA) encased in a protein coat called a capsid
- Some viruses have an additional lipid envelope surrounding the capsid (enveloped viruses)
- Enveloped viruses include influenza, HIV, and SARS-CoV-2
- Non-enveloped viruses include adenovirus and poliovirus
- Viral genomes can be single-stranded or double-stranded, and linear or circular
- Classified based on genome type, capsid symmetry, and presence of an envelope
- Baltimore classification system categorizes viruses into seven groups based on genome type and replication strategy
- Range in size from ~20 nm (parvovirus) to ~400 nm (mimivirus)
- Capsid proteins self-assemble to form icosahedral, helical, or complex symmetries
- Icosahedral symmetry is common among many viruses (adenovirus, poliovirus)
- Helical symmetry is found in viruses like tobacco mosaic virus and influenza virus
Viral Entry and Replication
- Viruses must enter host cells to initiate replication
- Entry mechanisms vary depending on the virus and host cell type
- Enveloped viruses fuse with the host cell membrane to release their genome
- Non-enveloped viruses penetrate the cell membrane or undergo receptor-mediated endocytosis
- Viral attachment proteins (VAPs) bind to specific receptors on the host cell surface
- HIV uses CD4 and CCR5/CXCR4 as receptors
- Influenza virus binds to sialic acid residues
- Following entry, viruses hijack host cell machinery to replicate their genome and synthesize viral proteins
- Viral replication strategies depend on the genome type (DNA or RNA)
- DNA viruses typically replicate in the nucleus using host cell enzymes
- RNA viruses replicate in the cytoplasm using viral RNA-dependent RNA polymerase
- Positive-sense RNA viruses (poliovirus) can directly serve as mRNA for protein synthesis
- Negative-sense RNA viruses (influenza) require viral RNA polymerase to synthesize positive-sense RNA
- Viral assembly occurs in the cytoplasm or at the cell membrane
- Newly formed virions are released by cell lysis or budding from the cell membrane
Host Cell Interactions
- Viruses rely on host cell factors and pathways for successful replication
- Hijack host cell transcription and translation machinery to produce viral proteins
- Some viruses (influenza) shut down host cell protein synthesis to prioritize viral protein production
- Manipulate host cell signaling pathways to create a favorable environment for replication
- HIV activates NF-κB pathway to enhance viral gene expression
- Alter host cell metabolism to support viral replication
- Hepatitis C virus induces lipid accumulation in infected cells
- Induce cell cycle arrest or apoptosis to facilitate viral spread
- Adenovirus E1A protein induces cell cycle progression to S phase
- Interfere with host cell antiviral defenses
- Herpes simplex virus ICP34.5 protein inhibits protein kinase R (PKR) activation
- Exploit host cell cytoskeleton for viral transport and assembly
- Vaccinia virus uses microtubules for intracellular transport
- Modulate host cell gene expression to enhance viral replication and evade immune responses
- Epstein-Barr virus EBNA2 protein activates host cell genes involved in cell growth and survival
Immune Response to Viral Infections
- Innate immune response provides the first line of defense against viral infections
- Type I interferons (IFN-α/β) are produced by infected cells and stimulate antiviral state in neighboring cells
- Natural killer (NK) cells recognize and kill virus-infected cells
- Pattern recognition receptors (PRRs) detect viral components and initiate innate immune signaling
- Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs) are key PRRs in antiviral immunity
- Adaptive immune response is virus-specific and develops over time
- CD8+ T cells (cytotoxic T lymphocytes) directly kill virus-infected cells
- CD4+ T cells (helper T cells) support B cell and CD8+ T cell responses
- B cells produce virus-specific antibodies that neutralize viral particles and prevent infection of new cells
- Antibodies can also facilitate phagocytosis and complement-mediated lysis of viruses
- Memory B and T cells provide long-lasting protection against future infections with the same virus
- Cytokines and chemokines coordinate the immune response and attract immune cells to the site of infection
- IL-12 and IFN-γ promote T cell differentiation and activation
- CXCL10 attracts T cells and NK cells to infected tissues
Viral Evasion Strategies
- Viruses have evolved various mechanisms to evade or suppress the host immune response
- Antigenic drift and shift allow viruses (influenza) to escape antibody recognition
- Antigenic drift involves minor changes in viral surface proteins due to mutations
- Antigenic shift occurs when two different influenza strains exchange genetic material, resulting in a novel strain
- Viral proteins can interfere with innate immune signaling pathways
- Hepatitis C virus NS3/4A protease cleaves and inactivates MAVS, a key adaptor protein in RLR signaling
- Inhibit antigen presentation to T cells by downregulating MHC class I expression
- Human cytomegalovirus (HCMV) US2 and US11 proteins target MHC class I for degradation
- Produce decoy receptors that sequester antiviral cytokines
- Vaccinia virus secretes a soluble IFN-γ receptor to neutralize the effects of IFN-γ
- Induce apoptosis of immune cells to suppress the immune response
- HIV Nef protein induces apoptosis of CD4+ T cells
- Establish latent infections to avoid immune detection
- Herpes simplex virus establishes latency in sensory neurons
- Rapidly mutate to generate escape variants that are not recognized by the immune system
- HIV and hepatitis C virus have high mutation rates due to error-prone replication
Disease Manifestation and Progression
- Viral infections can cause a wide range of clinical manifestations, from asymptomatic to severe disease
- Incubation period is the time between initial infection and the appearance of symptoms
- Varies depending on the virus and host factors
- Influenza has a short incubation period (1-4 days), while HIV can have a long incubation period (years)
- Acute infections are characterized by rapid onset of symptoms and viral replication
- Common cold caused by rhinoviruses typically lasts 7-10 days
- Chronic infections persist for extended periods and can lead to long-term complications
- Hepatitis B and C viruses can cause chronic liver disease and cirrhosis
- Viral tropism determines the cell types and tissues targeted by the virus
- Measles virus primarily infects respiratory epithelial cells and immune cells
- Zika virus has a tropism for neural progenitor cells, leading to microcephaly in infants
- Viral load and host immune response influence disease severity
- High viral loads are often associated with more severe symptoms
- Immunocompromised individuals are at higher risk for severe disease
- Co-infections with multiple viruses or with bacteria can exacerbate disease severity
- HIV-infected individuals are more susceptible to opportunistic infections like Pneumocystis pneumonia
- Long-term sequelae can occur after viral clearance
- Chikungunya virus infection can lead to chronic joint pain and arthritis
Viral Transmission and Epidemiology
- Viruses can be transmitted through various routes, depending on the virus and host factors
- Respiratory transmission occurs via droplets or aerosols (influenza, SARS-CoV-2)
- Fecal-oral transmission involves ingestion of contaminated food or water (norovirus, rotavirus)
- Vector-borne transmission relies on insects or arthropods (dengue virus, Zika virus)
- Sexual transmission occurs through sexual contact (HIV, HPV)
- Viral shedding is the release of infectious virions from an infected host
- Shedding can occur before, during, or after symptom onset
- Asymptomatic individuals can still shed virus and contribute to transmission
- Reproductive number (R0) represents the average number of secondary infections caused by one infected individual
- R0 > 1 indicates potential for epidemic spread
- R0 is influenced by factors such as population density, immunity, and social behaviors
- Herd immunity occurs when a significant proportion of the population is immune, reducing the likelihood of outbreak
- Can be achieved through natural infection or vaccination
- Zoonotic viruses are transmitted from animals to humans
- Ebola virus and SARS-CoV originated from bats
- Viral evolution and emergence of novel strains can lead to pandemics
- 2009 H1N1 influenza pandemic resulted from reassortment of human, swine, and avian influenza viruses
- Epidemiological studies help identify risk factors, transmission patterns, and effective control measures
- Contact tracing is used to identify and isolate exposed individuals to limit spread
Treatment and Prevention Approaches
- Antiviral drugs target specific stages of the viral life cycle to inhibit replication
- Nucleoside analogues (acyclovir) inhibit viral DNA synthesis
- Protease inhibitors (lopinavir) block viral protein maturation
- Entry inhibitors (maraviroc) prevent viral attachment or fusion
- Combination therapy using multiple antivirals can improve efficacy and reduce resistance development
- Highly active antiretroviral therapy (HAART) for HIV treatment
- Monoclonal antibodies can be used for prophylaxis or treatment
- Palivizumab is used to prevent respiratory syncytial virus (RSV) infection in high-risk infants
- Vaccines are the most effective means of preventing viral infections
- Live attenuated vaccines contain weakened viruses that induce immunity (MMR vaccine)
- Inactivated vaccines use killed viruses to stimulate an immune response (influenza vaccine)
- Subunit vaccines contain specific viral antigens (hepatitis B vaccine)
- Nucleic acid vaccines deliver viral genes to host cells for antigen production (COVID-19 mRNA vaccines)
- Vaccine development involves extensive testing for safety and efficacy
- Clinical trials progress from small-scale safety studies to large-scale efficacy trials
- Post-marketing surveillance monitors for rare adverse events and long-term effectiveness
- Infection control measures help prevent viral transmission
- Hand hygiene, personal protective equipment (PPE), and disinfection of surfaces
- Isolation of infected individuals and quarantine of exposed contacts
- Public health interventions aim to reduce viral spread at the population level
- Health education campaigns promote risk reduction behaviors
- Travel restrictions and border controls can limit international spread during outbreaks
- Global surveillance networks monitor viral circulation and emergence of novel strains
- World Health Organization (WHO) coordinates international response to viral outbreaks