Within every cell exists a silent security system known as intrinsic immunity, a fundamental layer of defense against viruses. This system consists of specialized proteins, encoded by the host’s genes, that are always present and ready to act. Unlike other parts of the immune system that need activation, intrinsic immunity provides an immediate, pre-existing barrier to intercept viruses at the earliest stages of infection. Its primary function is to directly interfere with a virus’s ability to replicate and spread, halting an infection before it can take hold.
Intrinsic Immunity’s Unique Place in the Immune System
The body’s defense network has two main branches: innate and adaptive immunity. Intrinsic immunity carves out its own distinct space, sharing features with both but remaining mechanistically separate. Like the innate system, it provides a rapid, first-response capability. Innate immunity, however, relies on recognizing broad molecular patterns to trigger a wider inflammatory response.
In contrast, intrinsic immunity employs specific proteins called restriction factors, which are present at constant levels within cells to act against particular viruses. This specificity is conceptually similar to adaptive immunity, which also targets individual pathogens. However, intrinsic immunity lacks the “memory” that is the hallmark of the adaptive system and does not learn from past encounters.
While the adaptive immune response can take days to mobilize, intrinsic factors are effective immediately upon a virus’s entry into the cell. This is important for combating retroviruses like HIV, which quickly integrate their genetic material into the host cell’s genome. By acting instantly, intrinsic immunity can prevent this integration from ever occurring.
How Intrinsic Immunity Operates
Restriction factors use diverse strategies that target precise stages of viral replication. One common tactic is blocking a virus from entering a cell or releasing its genetic material. Other factors work by disrupting the replication of the viral genome, preventing the virus from making copies of its genetic instructions.
A different approach involves interfering with the later stages of infection. Certain intrinsic factors can hamper the assembly of new virus particles so they cannot be put together correctly. Another strategy involves preventing newly formed viruses from budding off and leaving the host cell to infect others.
While many of these restriction factors are always present, their levels can be boosted by signaling molecules like interferons. This links them to the broader innate immune response but underscores their direct antiviral role.
Notable Intrinsic Factors and Their Viral Targets
Several notable restriction factors illustrate how this system works in practice.
- APOBEC3G: This factor targets retroviruses like HIV by chemically altering DNA building blocks. It introduces numerous mutations into the viral DNA during replication, rendering the resulting genomes unable to produce viable new viruses.
- TRIM5α: This protein recognizes the capsid, the protective coat around viral genetic material. It binds to the incoming capsid of viruses like SIV and prevents the virus from “uncoating” to release its contents. The version in rhesus monkeys is effective against HIV, while the human version is not.
- Tetherin (BST-2): This protein prevents newly formed enveloped viruses like HIV and influenza from escaping the cell. As virus particles try to bud from the cell surface, Tetherin acts as a molecular rope, trapping the virus and preventing its spread.
- SAMHD1: This protein restricts HIV in certain immune cells by depleting the supply of deoxynucleoside triphosphates (dNTPs). These molecules are the building blocks retroviruses need to build their DNA, so reducing them starves the virus of resources required for replication.
The Evolutionary Arms Race: Intrinsic Immunity vs. Pathogens
The constant pressure from intrinsic immunity has forced viruses to evolve countermeasures, creating a dynamic evolutionary arms race. For every restriction factor that blocks a viral process, viruses develop sophisticated strategies to evade or disable these defenses. This conflict drives the evolution of both host proteins and viral mechanisms.
A classic example is the interaction between the HIV protein Vif and the human restriction factor APOBEC3G. To counter APOBEC3G’s ability to mutate the HIV genome, HIV evolved the Vif protein. Vif finds APOBEC3G and tags it for destruction by the cell’s own disposal system, allowing the virus to replicate.
Similarly, viruses have found ways to defeat Tetherin. Some viruses produce proteins that directly target and degrade Tetherin. Others have evolved mechanisms to block its function, severing the molecular rope that holds them to the cell surface.
This struggle leads to rapid changes in the genes for restriction factors, resulting in variations between closely related species. The ongoing conflict shapes the evolution of viruses and their hosts. It also influences which species a virus can infect and how severe the resulting disease will be.