Intrinsic immunity
Intrinsic immunity refers to a set of
Background
Eukaryotic organisms have been exposed to viral infections for millions of years. The development of the innate and adaptive immune system reflects the
The recognition of intrinsic immunity as a potent anti-viral defense mechanism is a recent discovery and is not yet discussed in most immunology courses or texts. Though the extent of protection intrinsic immunity affords is still unknown, it is possible that intrinsic immunity may eventually be considered a third branch of the traditionally bipartite immune system.[citation needed]
Relationship to the immune system
Intrinsic Immunity combines aspects of the two traditional branches of the immune system – adaptive and innate immunity – but is mechanistically distinct. Innate cellular immunity recognizes viral infection using
Unlike adaptive and innate immunity, which must sense the infection to be turned on (and can take weeks to become effective in the case of adaptive immunity) intrinsic immune proteins are constitutively expressed and ready to shut down infection immediately following viral entry. This is particularly important in retroviral infections since
Because the production of intrinsic immune mediating proteins cannot be increased during infection, these defenses can become saturated and ineffective if a cell is infected with a high level of virus.[citation needed]
Activities of canonical intrinsic immune proteins
- rhesus monkey TRIM5α variant is able to recognize and prevent HIV infection, whereas the human TRIM5α protein can prevent SIV infection. This variation helps explain why HIV and SIV infect humans and monkeys respectively, and probably reflects a previous epidemic of what we now call HIV among ancestors of current rhesus monkey populations.[3]
- mutations to be viable. APOBEC3G expression is disrupted by the HIV vif protein which induces its degradation through the ubiquitin/proteasome system. Vif actually exploits our intrinsic immunity, titrating the degree of APOBEC3G polyubiquitination in order to augment the genetic variability already present in HIV-1 (owing to its mutation-happy reverse transcriptase). Vif therefore acts via APOBEC3G to increase the likelihood of the generation of escape mutants in HIV-1 pathogenesis. If an HIVΔvif deletion mutant is created it will be able to infect a cell, but will produce non-viable progeny virus due to the action of APOBEC3G.[4]
Other intrinsic immune proteins have been discovered which block