Viral Epitope Escape in Acute HIV-1 Infection

The human immunodeficiency virus (HIV) is a lentivirus that infects and damages the immune system, ultimately resulting in the development of acquired immunodeficiency syndrome. A key feature of the HIV is its ability to rapidly mutate during the course of infection, which allows it to evade the immune response. In the case of the CD8+ cytotoxic T lymphocyte (CTL) response, it has been shown that there is strong selection for viral mutations in T cell epitopes, resulting in the sequential emergence of antiviral CTL to different epitopes over time. This epitope escape from virus-targeted CTL responses occurs rapidly after acute infection and contributes to the eventual failure of effective immune control of HIV-1 infection. Understanding this process of epitope escape and subsequent immune failure is critical for HIV-1 vaccine design. In the current issue of Viral Immunology, Kim and colleagues have systematically identified CD8+ T lymphocyte responses during acute infection and correlated the progression of these immune responses to the evolution of viral epitope variants. Their data provide a detailed picture of the CD8+ CTL response during a period of dynamic active viral evolution in acute HIV-1 infection. The authors note that this approach can be applied to future studies involving larger cohorts of acutely infected individuals to give more insight into how clonal breadth, the development of new CTL responses, and other factors, such as the CD4+ T cell response, influence epitope escape.

In a separate study focused on the dynamics of T cell responses to HIV, Negi et al. have undertaken a longitudinal analysis of the proliferation and frequencies of different T cell subsets in HIV-1-infected Indian patients stratified as rapid, viremic slow, or slow progressors. Their data demonstrate distinct dynamics for CD4+ and CD8+ T cell subsets depending on the nature of the infection. Of note, an increase in central memory T cell proliferation in viremic slow and slow progressors could be attributed to the slower progression of the HIV infection. The authors suggest that treatment strategies should focus on restoring the homeostatic balance of T cell subsets to restore T cell functionality.

Two articles in this issue of Viral Immunology focus on the adaptive immune responses to two more clinically important viruses that have the capacity to establish persistent infections. Chang and colleagues have analyzed the antibody response to hepatitis B virus (HBV) infection with a view to improving our understanding of how they can neutralize the virus. Their study provides insights into the structural basis of interactions between an antibody and the pre-S2 epitope of the HBV surface antigen. Kumar et al. report on the development of a new vaccine for Ebolavirus (EBOV) infection based on a human adenovirus that expresses an EBOV glycoprotein. The vaccine was strongly immunogenic in mice and is a candidate for further characterization and development.

Epstein Barr virus (EBV) is another clinically important virus that can establish a persistent infection. EBV infection is linked to Graves' disease, an autoimmune hyperthyroidism that predominantly affects women. Interestingly, pregnancy can transiently reduce the symptoms of the disease, although the underlying mechanisms are unknown. Hara and colleagues report that a female steroid hormone (estradiol) modulates production of thyrotropin receptor antibody, an etiological factor attributed to Graves' disease. The data provide a possible explanation for premenstrual worsening and maternal improvement of autoimmune disease in general, including Graves' disease.

Finally, the current issue also includes a letter to the editor from Wang and colleagues about the potential roles of ADAR1 (adenosine deaminase acting on RNA), an RNA editing enzyme, in the regulation of antiviral immunity.

I would like to thank all of the authors for their excellent contributions to the Journal and all of the reviewers who work tirelessly to ensure high quality of published articles.