How Viruses Aid the Evolution of Adaptive Immune System in Mammals

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Innate immunity responds similarly to every pathogen. It is already “in-place” since birth; so, in this way, it’s innate. Because it is the first line of defense, it participates in the general elimination of pathogens. Most importantly, it signals and activates the adaptive arm of the immune system.

• Examples of innate immunity include the skin barrier, stomach acid, enzymes in tears, sneeze reflex, and certain white blood cells like neutrophils and macrophages.

Adaptive immunity responds differently to each pathogen. As follows, it needs time “to prepare” and only comes in when innate immunity fails. Because of its precision, it participates in the “search-and-destroy” of specific pathogens. It also memorizes previous encounters of pathogens — enabling quicker response when it sees the same pathogen again; so, in this way, it adapts.

• Examples of adaptive immunity include leukocytes called T-cells and B-cells.

Evolution of Adaptive Immunity

Because adaptive immunity is much more specific and complex, it evolved much later and first appeared ~500 million years ago in jawless vertebrates — hagfish and lamprey.

Since then, all jawed animals have adaptive immunity, whereas innate immunity is present “at almost every level of the evolutionary tree of life,” said Professor Max D. Cooper, a medical doctor and professor of pathology at Emory University who is known for the discovery of T-cells and B-cells.

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“The survival advantage gained through adding this type of adaptive immune system to a pre-existing innate immune system led to the evolution of alternative ways for lymphocytes to generate diverse antigen receptors for use in recognizing and repelling pathogen invaders,” explains Professor Cooper.

This means that the adaptive immune system is the “more evolved” immunity that allows organisms to fight more diverse types of pathogens. Without adaptive immunity, it’s game over once pathogens manage to pass through the first line of defense (i.e., innate immunity). Scientists call this immunodeficiency, which can apply to both innate and adaptive immunity.

How did adaptive immunity evolve?

Superinfection Exclusion in Plants

This is best demonstrated with tobacco plants wherein pre-infection with a mild type of Tobacco mosaic virus (TMV) protects against the virulent type of TMV. Isn’t this similar to how vaccines — which rely on the memory of the adaptive immune system — work?

“Thus, superinfection exclusion can be regarded as a simple adaptive immune system,” Felix Broecker, a microbiologist at the Icahn School of Medicine at Mount Sinai, writes in a 2019 paper titled “Evolution of Immune Systems From Viruses and Transposable Elements.”

Superinfection exclusion, however, doesn’t tell much about how adaptive immunity came to be. Plants don’t have an adaptive immune system after all. But it does tell us how viruses have contributed to adaptive-like immunity in the Plantae kingdom of the tree of life.

Superinfection Exclusion-Like System in Animals

A virus’s life cycle, by default, involves injecting its genetic material into the cell genome. About 8% of the human genome consists of retrovirus sequences — which have been “repurposed” for the survival advantage of the host.

A prime example of this is the syncytin gene — obtained from a retrovirus — that enables the formation of the placenta in the animal kingdom. This theory has been supported by rigorous experimental and bioinformatics studies.

The same trend is observed with the Fv4 gene derived from the murine leukemia virus. Mice who have this gene are, in turn, immune to murine leukemia viruses. Another example is the Rmcf gene that provides resistance against MCF (mink cell focus-inducing) viruses. Similarly, sheep with the JSRV gene are protected against the JSRV virus. The same is seen with certain viruses (retro- or not) affecting cats, koalas, horses, cattle, squirrels, primates, insects, and human cell lines.

Remove or silence these virus genes and these animals or human cells become susceptible to infection by the respective viruses. Nature has also shown this: Koalas in Queensland are more prone to virus infection than koalas from other parts of the world because of a weaker version of the KoRV (koala-retrovirus) gene.

How did these virus sequences confer protection? Experimental evidence suggests it has something to do with blockage wherein the virus occupies the same receptor or genomic position — preventing any opportunity for other viruses of the same type. This system is similar to superinfection exclusion wherein a prior infection with a virus (that became integrated into the host genome) protects the host against a similar type of virus.

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Activating Adaptive Immunity

Perhaps the most direct contribution of endogenized (or integrated) retroviruses to adaptive immunity lies in their ability to activate and regulate it.

The “enhancer sequence” that activates the interferon production is also a retroviral sequence. Interferons interfere with virus replication by activating both innate and adaptive immunity. “This suggests that endogenous retroviral sequences have been specifically adopted by host cells to modulate interferon responses, a major branch of the antiviral immune defense,” Broecker explains.

Adaptive T-cells can also be activated by MHC proteins. When a cell becomes infected, it displays the foreign molecule on its surface MHC protein — in a process called antigen presentation — to signal T-cells to destroy it. The genes that code for MHC proteins are also largely derived from retroviruses.

Adaptive B-cells secrete diverse types of antibodies catered to a specific pathogen. This antibody production depends on a complex recombination system. Enzymes that power this system may have originated from retroviruses’ enzymes, scientists think but it’s still debatable, Broecker said.

Nonetheless, ancient viruses (especially retroviruses) have contributed to the adaptive immune response to today’s pathogenic viruses. “Given their diverse roles in various immune systems, it appears that recruitment of [virus sequences] for antiviral defense mechanisms has been a major driving force in the evolution of cellular life,” Broecker said in a concluding statement.

This article was originally published in Microbial Instincts with minor modifications.

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