Genetics and Evolution

Molecular Basis of Inheritance

Genome Organization in Viruses

Viruses: An Introduction

  • Non-living infectious agents
  • Consist of genetic material (DNA or RNA) surrounded by a protein coat
  • Cannot replicate on their own, require host cells for replication
  • Can infect different species of organisms

Genome Organization in Viruses

Viruses have different types of genome organization:

  1. DNA Viruses: Have DNA as their genetic material
    • Can be single-stranded (ssDNA) or double-stranded (dsDNA)
  1. RNA Viruses: Have RNA as their genetic material
    • Can be single-stranded (ssRNA) or double-stranded (dsRNA)
  1. Retroviruses: Have RNA as their genetic material, but replicate via reverse transcription (RNA → DNA)
    • Example: HIV

Types of DNA Viruses

  1. Single-stranded DNA (ssDNA) Viruses:
    • Example: Parvovirus
  1. Double-stranded DNA (dsDNA) Viruses:
    • Example: Adenovirus, Herpesvirus

Types of RNA Viruses

  1. Single-stranded RNA (ssRNA) Viruses:
    • Positive-sense ssRNA viruses (direct mRNA)
      • Example: Rhinovirus, Zika virus
    • Negative-sense ssRNA viruses (complementary to mRNA)
      • Example: Influenza virus, Measles virus
  1. Double-stranded RNA (dsRNA) Viruses:
    • Example: Reovirus

Genome Organization in Different Viruses

  1. Linear Genome:
    • Genetic material in a linear arrangement
    • Example: Poliovirus
  1. Circular Genome:
    • Genetic material in a circular arrangement
    • Example: Papillomavirus
  1. Segmented Genome:
    • Genetic material divided into separate pieces (segments)
    • Example: Influenza virus

Types of Genetic Material in Viruses

  1. Non-segmented Genomes:
    • Genetic material not divided into segments
    • Example: HIV, Hepatitis B virus
  1. Segmented Genomes:
    • Genetic material divided into multiple segments
    • Example: Influenza virus

Non-segmented Genomes

  • Non-segmented genomes can be either:
    1. Monopartite:
      • Entire genetic material present in a single piece
      • Example: HIV
    2. Dipartite:
      • Genetic material divided into two separate pieces
      • Example: Hepatitis B virus

Segmented Genomes

  • Segmented genomes consist of separate pieces of genetic material called segments
  • Each segment can encode different functional units or genes
  • Example: Influenza virus has 8 separate RNA segments

Importance of Genome Organization in Viruses

  • Genome organization affects various aspects of viral biology, including:
    • Replication and transcription processes
    • Genetic variability and evolution
    • Interaction with host immune system
    • Potential for recombination and reassortment

Replication in DNA Viruses

  • DNA synthesis occurs within the infected host cell.
  • The viral DNA serves as a template for the synthesis of new viral DNA.
  • This process is carried out by viral enzymes.
  • Example: Adenovirus uses the host DNA polymerase for replication.

Replication in RNA Viruses

  • RNA synthesis can occur within the viral capsid or in the host cell’s cytoplasm.
  • Viral RNA polymerase catalyzes the synthesis of viral RNA from a template.
  • Positive-sense RNA viruses can directly produce viral proteins, acting as mRNA.
  • Negative-sense RNA viruses require the synthesis of complementary mRNA strands.
  • Example: Influenza virus uses its RNA polymerase for replication.

Genetic Variability in Viruses

  • Viruses show high genetic variability due to:
    • High mutation rates during replication
    • Recombination events between different strains
    • Reassortment of genetic material in segmented genomes
  • This helps viruses adapt to changing environments and evade host immune responses.
  • Example: Influenza virus mutates rapidly, leading to the emergence of new strains.

Genetic Variation and Evolution

  • Genetic variations in viruses can lead to the emergence of new strains.
  • Selection pressures, such as host immune responses, drive the evolution of viral strains.
  • Evolutionary processes in viruses include:
    • Mutation: Random changes in the viral genome
    • Recombination: Exchange of genetic material between different viral strains
    • Natural selection: Favoring of beneficial genetic variations
  • Example: SARS-CoV-2 has undergone mutations, leading to the emergence of new variants.

Host Immune Response to Viral Infections

  • Innate immune response:
    • Activation of immune cells to mount a rapid defense against viruses
    • Release of cytokines and chemokines to recruit immune cells
  • Adaptive immune response:
    • Specific response against viral antigens by B and T cells
    • Production of antibodies targeting viral proteins
    • T cell-mediated destruction of infected cells
  • Example: Interferons released by infected cells help in limiting viral spread.

Viral Evasion of host Immune Responses

  • Viruses have evolved various mechanisms to evade host immune responses:
    • Mutations in viral proteins to avoid recognition by antibodies
    • Downregulation of major histocompatibility complex (MHC) molecules
    • Inhibition of interferon production or response
  • Example: HIV evades immune responses through high mutation rates and evasion of antibody recognition.

Recombination in Viruses

  • Recombination occurs when two genetically distinct viruses infect the same host cell.
  • Exchange of genetic material can occur, leading to the creation of novel viral strains.
  • Recombination is more common in viruses with segmented genomes.
  • Example: Hepatitis C virus undergoes frequent recombination events.

Antiviral Therapy

  • Antiviral drugs target specific steps in the viral life cycle, such as:
    • Inhibiting viral replication or transcription
    • Blocking viral entry into host cells
    • Impeding viral protein synthesis
    • Halting viral assembly or release
  • Example: Oseltamivir (Tamiflu) is used to treat influenza virus infections.

Vaccines and Viral Infections

  • Vaccines help prevent viral infections by inducing immunity against specific viruses.
  • Types of vaccines include:
    • Inactivated or attenuated viral vaccines
    • Subunit vaccines containing viral proteins
    • mRNA vaccines encoding viral antigens
  • Example: The polio vaccine is an inactivated viral vaccine.

Viral Zoonosis and Emergence of Pandemics

  • Zoonotic viruses are those that can be transmitted between animals and humans.
  • Cross-species transmission can lead to the emergence of pandemics.
  • Factors contributing to viral zoonosis include:
    • Changes in land use and animal-human interactions
    • Wildlife trade and consumption of exotic animals
  • Examples: SARS-CoV-2 (COVID-19) originated from animals, as did Ebola and Zika viruses. Here are slides 21 to 30 on the topic “Genetics and Evolution - Molecular Basis of Inheritance - Genome organization in viruses”:

Modes of Viral Transmission

Viruses can be transmitted through various routes:

  • Direct contact transmission:
    • Physical contact with an infected individual or their bodily fluids
    • Example: Influenza virus spreads through respiratory droplets.
  • Indirect contact transmission:
    • Touching surfaces contaminated with the virus
    • Example: Norovirus can be transmitted through contaminated food or water.
  • Vector-borne transmission:
    • Transmission through the bite of arthropod vectors, such as mosquitoes or ticks
    • Example: Dengue virus is transmitted by Aedes mosquitoes.
  • Airborne transmission:
    • Inhalation of infectious airborne particles
    • Example: Measles virus can be transmitted through airborne droplets.
  • Vertical transmission:
    • Passage of the virus from mother to fetus during pregnancy, or from parent to offspring
    • Example: Rubella virus can be transmitted from a pregnant woman to her unborn baby.

Host Range of Viruses

  • Viruses have specific host ranges, which determine the species they can infect.
  • Tissue tropism: Specific tissues or organs targeted by a particular virus.
  • Cell tropism: Specific types of host cells infected by a virus.
  • Example: Human Immunodeficiency Virus (HIV) mainly infects CD4+ T cells.
  • Zoonotic viruses: Viruses that can be transmitted between animals and humans.
  • Example: Avian Influenza viruses can infect both birds and humans.

Factors Influencing Viral Host Range

Several factors can influence the host range of viruses:

  • Viral Attachment Proteins: Viral proteins that determine the attachment or entry into host cells.
  • Cell Receptor Availability: Presence or absence of cellular receptors required for viral entry.
  • Host Factors: Availability of host factors necessary for viral replication or immune response.
  • Host Defense Mechanisms: Ability of the host immune system to recognize and eliminate viruses.

Factors Influencing Viral Transmission

Various factors can influence viral transmission:

  • Environmental Factors: Climate, temperature, humidity, and ecology of the habitat.
  • Host Behavior: Human activities impacting contact with infected individuals or vectors.
  • Immune Status: Immunocompromised individuals are more susceptible to viral infections.
  • Viral Stability: How long a virus can survive outside a host or in different environmental conditions.

Viral Replication Cycles

Viral replication involves several stages:

  1. Attachment: Virus attaches to specific receptors on the host cell surface.
  1. Entry: Virus enters the host cell, releasing genetic material into the cell.
  1. Replication: Viral genetic material replicates using host cell machinery.
  1. Assembly: Newly synthesized viral components assemble to form mature virions.
  1. Release: Mature virions are released from the host cell to infect other cells or hosts.

Viral Latency and Integration

  • Some viruses can establish a latent infection, remaining dormant within host cells.
  • Latent viruses can reactivate later to cause disease.
  • Examples:
    • Herpesviruses establish latency in nerve cells, causing recurrent outbreaks.
    • Human Immunodeficiency Virus (HIV) can integrate its genetic material into the host genome and remain latent in immune cells.

Major Viral Diseases

Several well-known viral diseases affect humans:

  • Influenza: Caused by the Orthomyxovirus family, leads to respiratory illness.
  • HIV/AIDS: Caused by Human Immunodeficiency Virus, leads to the progressive breakdown of the immune system.
  • Hepatitis: Caused by Hepatitis viruses (A, B, C, D, E), leads to inflammation of the liver.
  • Ebola: Caused by Ebola virus, leads to severe hemorrhagic fever.

Importance of Viruses

Viruses play significant roles in:

  • Evolution: Contributing to genetic diversity and shaping the genomes of organisms.
  • Medicine: Development of vaccines, antiviral drugs, and gene therapy techniques.
  • Biotechnology: Viral vectors used in gene transfer and genetic engineering.
  • Ecology: Impacting ecosystems through interactions with host organisms.

Virus Detection and Diagnosis

Methods used for virus detection and diagnosis:

  • Molecular Methods: PCR, RT-PCR, nucleic acid sequencing to detect viral genetic material.
  • Serological Methods: ELISA, Western blotting to detect viral antigens or antibodies.
  • Cultivation Methods: Growing viruses in cell cultures or animal models.
  • Microscopy: Electron microscopy for visualizing viral particles.

Conclusion

  • Viruses have diverse genome organizations and modes of replication.
  • Genetic variations and evolution drive the emergence of new viral strains.
  • Viruses interact with host immune responses and can evade or subvert them.
  • Understanding viral host range, transmission, and replication cycles is crucial for managing viral diseases.

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