Editorial: Host Immune Responses to Retroviral Infections

Abstract

Upon infection, retroviruses reverse transcribe their genome and integrate it into host chromosomes as proviruses; as such retroviruses are one of the greatest threats to the genetic integrity of all cellular organisms. At this point proviruses can hide inside host cells in a latent phase; however, when they are expressed and viral proteins are translated, their presence is recognized by the adaptive immune system. Thus, when inoculated into immunocompetent hosts, retroviruses can be rapidly eliminated and cause no pathology (1). To establish a long enough period of productive infection that allows interindividual transmission, retroviruses must overcome and/or evade host immune responses. Acutely transforming retroviruses overcome immune attacks by inducing rapid proliferation of infected cells, while non-acute retroviruses elaborate several different mechanisms to evade host immune responses and establish persistent infection. These mechanisms work through camouflaging viral particles, suppressing gene expression within infected cells, and inducing central and peripheral immune non-responsiveness. In this Research Topic, four groups of authors provide new insights into the different strategies that retroviruses have developed in the attempt to evade host immune responses and establish persistent infection. It has been known for a long time that when egressing from infected cells retroviruses incorporate host cell proteins into their envelope (reviewed in 2). This process is not just passive but some particular groups of host cell proteins are selectively incorporated from the plasma membrane into budding virions through interactions with viral proteins. Immunologically relevant examples of host cell proteins that are enriched in retroviral envelopes are MHC proteins, cell adhesion molecules and complement regulating factors (2). Using newly developed technique offlow virometry, Maltseva and Langlois have shown that the incorporation of tetraspanins and lipid raft-associated Thy1.2 andCD45 into Moloney murine leukemia virus (MuLV) particles is influenced by the presence or absence of the viral accessory protein, glycosylated Gag (glycoGag). GlycoGag is unnecessary for in vitro replication of MuLVs but is required for their efficient proliferation and pathogenicity in vivo, and glycoGag-deficient MuLV revert to glycoGag-expressing ones during in vivo propagation and tumorigenesis (3–5). GlycoGag is also implicated in the resistance of reverse transcription to the host restriction factor APOBEC3 (6). Thus, the paper by Maltseva and Langlois suggests that glycoGag may affect MuLV replication and pathogenesis not only through resistance to restriction factors but also by modulating incorporation of host-derived proteins into budding virions. As described above, non-acute retrovirusesmust evade host immune responses to establish persistent infection. Results by Higuchi et al. summarize HTLV-1’s strategies for evading immune responses,