Abstract
Retroviruses are major causes of disease in animals and human. Better understanding of the initial host immune response to these viruses could provide insight into how to limit infection. Mouse retroviruses that are endemic in their hosts provide an important genetic tool to dissect the different arms of the innate immune system that recognize retroviruses as foreign. Here, we review what is known about the major branches of the innate immune system that respond to mouse retrovirus infection, Toll-like receptors and nucleic acid sensors, and discuss the importance of these responses in activating adaptive immunity and controlling infection.
Highlights
The mammalian innate immune system serves as one of the first lines of defense against pathogens. It is composed of several receptors and signaling pathways involved in detecting foreign proteins, lipids, nucleic acid sequences or structures, and other components of pathogens, termed pathogen-associated molecular patterns (PAMPs)
TLR3, TLR9 and TLR3/9 KOs all produced wild-type levels of endogenous retrovirus (ERV)-specific antibodies when challenged with purified ERVs, whereas TLR7, TLR3/7, or Toll-like receptors (TLRs) 7/9 double or TLR3/7/9 triple KO mice were unable to produce ERV-specific antibodies. These results suggest that ERV replication intermediates generated during ERV reactivation are detected, that TLR7 is important for generating a protective antibody response, and that TLR3 and TLR9 modulate this response, leading to tumor rejection
One as-of-yet unsolved aspect of the role of TLR3, TLR7, or TLR9 in detecting retroviruses is that their ligand-binding domains are located within endosomes or on the cell surface, yet release of viral RNA and reverse transcription occurs within the cytoplasm upon infection
Summary
The mammalian innate immune system serves as one of the first lines of defense against pathogens It is composed of several receptors and signaling pathways involved in detecting foreign proteins, lipids, nucleic acid sequences or structures, and other components of pathogens, termed pathogen-associated molecular patterns (PAMPs). Several PRRs have been implicated in the antiviral innate response to murine retroviruses This is likely due to PAMPs that are generated at different times and places during the retroviral replication cycle. Retroviral replication produces different forms of nucleic acids, such as single-stranded (ss) RNA or DNA, RNA:DNA hybrids, and double-stranded (ds) RNA or DNA. These molecules are found in the cytosol, in subcellular compartments, and in the nucleus during replication and within endosomes when virus particles are engulfed [6] (Figure 1).
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