Viruses and Their Impact on Life

Viruses, Their Life Cycle, and Cancer

• Viruses are microscopic infectious agents containing DNA or RNA as genetic material.
• Viral genomes are enclosed within a protein coat called a capsid.
• Some viruses have an additional outer envelope containing glycoproteins.
• Viruses replicate only within a host cell, using the host's cellular machinery.

The Coronavirus Pandemic

• The human population has recently experienced a global pandemic caused by a virus.
• In early 2020, cases of COVID-19 reached pandemic levels.
• As of April 2024, 7 million people had died worldwide from COVID-19.

Viruses and the Tree of Life

• Viruses infect all forms of life, and every living organism has a virus that can infect it.
• Estimates suggest there are over 10 million times more viruses than stars in the universe.
• Each virus typically infects a few specific species (host range).
• Within a host, only a limited number of cell types will be infected by the virus (tropism).

What Are Viruses?

• Viruses are on the boundary of what biologists consider "life."
• They contain genetic material and are composed of protein capsids.
• They cannot replicate and use genetic information outside a living host cell.
• The host cell carries out all steps for viral DNA/RNA and viral protein synthesis.
• Large viruses have been discovered that possess molecules needed for translation.
• Mimivirus is an example of a large virus.

Viruses = Life?

• Mimivirus contains 7 of 67 universal genes shared among domains of life.
• Mimivirus encodes various proteins needed for translation and protein modification.
• Translation factors, tRNAs, and enzymes are also present in mimivirus.
• The "relics" of an ancestral protein translation apparatus have been gradually lost through a genome reduction.

Viruses: A Fourth Domain of Life?

• Some scientists hypothesize that viruses evolved from a fourth domain of life that has since disappeared.
• Viruses are perhaps merely escaped genetic fragments from hijacking genes from true organisms.
• Important enzymes in viruses may superficially resemble those of their hosts.
• However, DNA-replicating enzymes in viruses often bear no relation to host enzymes.

Virus Classification

• Viruses are classified based on their nucleic acid type (DNA or RNA), capsid symmetry (helical, icosahedral, head-and-tail), and presence or absence of an envelope.
• Viral genomes vary in size and structure (single-stranded, double-stranded, DNA, RNA)
• Baltimore classification classifies viruses based on their genome structure and replication strategy.

Virus Life Cycles

• Bacteriophages have a lytic cycle where progeny viruses are assembled, the host cell breaks open, and mature phages are released.
• Some bacteriophages have a lysogenic cycle where phage DNA is integrated into the host chromosome, Replication can occur, and the phage DNA is transmitted to progeny.
• Non-enveloped viruses adsorb to host cells. then undergo endocytosis. During the endocytosis step, the viral envelope is destroyed or the viral capsid is released
• Enveloped viruses have an outer membranous layer that fuses with the host membrane. Viral genomes are released in the cytoplasm and replicated Viral proteins are transcribed and translated, and assembled into new viruses which are released.

Virus Life Cycles: Non-enveloped Viruses (Poliovirus)

• Non-enveloped viruses depend on endocytosis.
• Viral genomes are released into the cytoplasm.
• Replication involves capturing host cellular machinery for genome replication and translation
• New viral copies are assembled and released from the cell.

Virus Life Cycles: Enveloped Viruses (HIV or Zikavirus)

• Enveloped viruses often fuse with the host membrane.
• Viral genomes are released into the cytoplasm.
• Replication involves capturing host cellular machinery.
• New viral copies are assembled and released from the cell.

Viruses That Cause Cancer

• 20% of human cancers are linked to viral infections.
• Cancer can result from the host's response to the viral infection or from the impact of viral genes on the host cell.
• Some viruses insert their genetic information into host chromosomes carrying oncogenes (cancer-causing genes).
• Other viruses disrupt the host cell's genes that regulate cell division.

RSV and the v-src Gene

• Viral genes can cause oncogenesis (the development of cancer).
• v-src, a viral gene in Rous sarcoma virus (RSV), is essential for oncogenesis.
• Mutant v-src forms cause proteins to interact with host cell proteins
• Normal avian cells carry a gene (c-src) similar to v-src
• Sequences of c-src and v-src are different, and the protein function of c-src is different

Oncogenesis

• Cancer is a genetic disease involving mutations in genes that control cell growth and division.
• Oncogenesis results in tumors
• Tumors are composed of rapidly dividing cells that may invade neighboring tissues.
• Cancer development can be caused by inherited mutations, DNA damage from environmental agents, or viral infections.

Viruses That Can Cause Cervical Cancer

• Certain types of human papillomavirus (HPV) infection can lead to cervical cancer.
• HPV integrates its DNA into the host cell DNA, and can cause cancer.

The Cell Cycle

• The cell cycle is a regulated process that controls cell growth, DNA synthesis, and cell division.
• Interphase (includes G1, S, and G2 phases) is the period where the cell is not actively dividing
• M phase (includes mitosis and cytokinesis) is when the cell divides

DNA Damage Checkpoints

• Cells have checkpoints to monitor for DNA damage to prevent errors
• p53 is a protein activated by DNA damage that inhibits the cell cycle.

HPV Encodes Tumor Suppressors

• HPV E6/7 proteins bind and inactivate the p53 tumor suppressor.
• This allows cells with damaged DNA to divide, which can lead to oncogenesis.

Proto-oncogenes and Tumor Suppressors

• Proto-oncogenes are normal genes that can become oncogenes (cancer-causing genes) upon mutation.
• Tumor suppressors are genes that control cell division,
• Mutations in tumor suppressors can lead to uncontrolled cell growth.

Multiple-Mutation Model for Cancer Development

• Most human cancers develop from the accumulation of mutations in proto-oncogenes or tumor suppressor genes.
• Mutations can lead to benign or metastatic cancer depending on the number and type of mutations.

Take-home Thoughts

• The study of viruses and virus-induced cancers deepens our understanding of cellular mechanisms.
• Viruses demonstrate varied integration into the tree of life, challenging traditional definitions.