Viruses are microscopic entities that cannot replicate on their own. They consist of genetic material, either DNA or RNA, encased within a protein coat. To reproduce, viruses must infect living cells and utilize host cell machinery. Host cell DNA, the genetic blueprint, contains instructions for cellular functions. Viruses interact with and often compromise this host DNA, manipulating cellular processes for their own survival.
Viral Invasion and Replication
Viral infection begins when a virus attaches to a host cell by recognizing receptor molecules. Following attachment, the virus or its genetic material enters the cell, and the viral genetic material is released through uncoating. Once inside, viruses hijack host cell resources, including ribosomes, enzymes, and nucleotides, to replicate their own genetic material and synthesize viral proteins.
This process often manipulates host cell nuclear components. DNA viruses typically enter the nucleus to access host DNA replication and transcription machinery. RNA viruses, while primarily replicating in the cytoplasm, can still influence nuclear processes to facilitate their life cycle. This commandeering sets the stage for interactions that compromise host genetic integrity.
Direct Assault on Host DNA
Some viruses directly damage host DNA through specific molecular mechanisms. Certain viruses encode nucleases, enzymes that degrade host cell DNA into smaller fragments. This action prevents normal host cell function and provides nucleotides for new viral genetic material. For instance, bacteriophages like T4 and T7 produce nucleases that break down bacterial chromosomes, with over 80% of T7 progeny DNA nucleotides sometimes sourced from degraded host DNA.
Genomic integration is another direct method, where certain viruses insert their genetic material into host cell DNA. Retroviruses, such as HIV, employ integrase to insert a DNA copy of their RNA genome into host chromosomes. This integration can disrupt critical host genes, potentially inactivating tumor suppressor genes or activating oncogenes, which promote uncontrolled cell growth. The inserted viral DNA, a provirus, becomes a permanent part of the host cell’s genome, replicated along with it.
Viruses can also directly interfere with host cell DNA replication and repair machinery. Viral proteins may bind to host enzymes involved in these processes, inhibiting their function or redirecting them for viral replication. For example, certain viral proteins can disrupt host helicases, enzymes that unwind DNA for replication, forcing host machinery to prioritize viral DNA synthesis. Other viral proteins, like those from HPVs or HIV Vpr, directly interact with and compromise components of host DNA damage response pathways, preventing proper repair of the host genome.
Indirect Disruption of DNA Integrity
Beyond direct attacks, viruses can compromise host DNA integrity indirectly, often by triggering cellular stress responses or manipulating cell cycle progression. Viruses can induce programmed cell death, known as apoptosis, in the host cell. While apoptosis is a natural host defense to eliminate infected cells, viruses can manipulate this process. During apoptosis, host cell enzymes like caspases and endonucleases fragment DNA, leading to cell demise.
Many viruses produce proteins that interfere with host cell DNA repair mechanisms. Disabling these repair systems allows existing DNA damage, whether viral or from other cellular stresses, to accumulate. This accumulation leads to genomic instability, resulting in cellular dysfunction or cell death. For instance, HCV core protein can bind to and inhibit components of the DNA repair machinery, while HTLV-1 Tax protein interferes with multiple repair pathways.
Viruses also commonly manipulate host cell cycle progression. They can force cells into specific cell cycle phases, such as S phase (DNA synthesis), to access host replication machinery for viral genome duplication. This manipulation can lead to DNA damage by forcing replication under abnormal conditions or overriding checkpoints that monitor DNA integrity.
Impact on the Host Cell
The destruction or compromise of host DNA by viral action has significant consequences for the infected cell. A common outcome for infected cells is cell death, often through lysis, where the cell membrane ruptures, releasing viral particles. This disruption prevents the cell from performing its functions.
Even if the cell does not die, compromised host DNA means it can no longer perform specialized tasks effectively, leading to loss of function within tissues or organs. This cellular dysfunction can contribute to the symptoms and pathology of viral diseases. Ultimately, manipulating and destroying host DNA serves the virus’s goal of efficient replication and propagation.
In some cases, particularly with viruses that integrate their genetic material into the host genome, DNA damage can lead to cellular transformation. This involves uncontrolled cell growth and division, potentially contributing to the development of cancers. Continued presence of viral genetic material and its disruptive effects on host DNA can alter cellular regulation, setting the stage for long-term health issues.