Immune Responses to HIV

Human Immunodeficiency Virus (HIV) remains a major clinical problem, responsible for approximately 1.5 million deaths around the globe every year. Yet, despite several decades of intensive research, an effective vaccine remains elusive. One of the key reasons is genetic instability of the virus and its complex interplay with, and evasion of, the immune system. The current issue of Viral Immunology features three important articles that address different aspects of the immune response to HIV. Joedicke and colleagues point out that regulatory T cells (Tregs) play an important role in the pathogenesis of HIV-1 infection. Since these cells frequently express the chemokine receptor CCR5, the authors investigated whether antiretroviral treatment with the CCR5 antagonist Maraviroc affected Tregs in chronically HIV-1-infected individuals. Their data indicate that the frequency and the activation status of Tregs in patients effectively treated with antiretroviral drugs were comparable to those of healthy individuals. The underlying mechanism reflected Maraviroc's control of viral replication rather than a direct binding of Maraviroc to CCR5-positive Tregs. Tanaskovic et al. have also studied immunity in patients on antiretroviral therapy, specifically measuring CD4 T cell numbers. After 9 months, treated patients had fewer naive CD4 T cells and more memory CD4 T cells than controls. Their data suggest that the ongoing immune activation may reduce the naive T cell pool and drive the accumulation of memory cells. Cytotoxic CD8+ T lymphocytes (CTLs) are also critical in cellular immune responses. Kang and colleagues have analyzed HIV-specific CTLs in HIV-infected individuals and show that the size of the response correlates with the size of the HIV-1 reservoir. The authors suggest that the HIV-1-specific CTLs response might be a biomarker for the efficacy of antiviral therapy.

Morbidity and mortality in the elderly are associated with viral infections, including influenza and cytomegalovirus (CMV). Theeten et al. point out that insights into the association between immunity against influenza and CMV will advance our understanding of healthy aging. The authors analyze influenza-vaccinated elderly patients and show that those with cellular immunity against CMV were more likely to develop cellular immunity against the influenza vaccine N1 antigen. These findings emphasize the importance of exploring the possible role of CMV in immunosenescence. Also on the vaccination front, Gohil et al. have investigated the prevalence of IgG antibodies against measles, mumps, and rubella among college students. The proportion of individuals seronegative for measles and rubella was relatively high in this reproductive age group, suggesting that a dose of measles–rubella vaccine should be offered to these young adults. Hepatitis C virus (HCV) infection is considered as one of the most significant international health concerns, yet a vaccine has not yet been developed. Behzadi and colleagues have evaluated the immunogenicity of a DNA vaccine candidate for HCV, based on nonstructural proteins NS3/NS4A in C57BL/6 mice. The vaccine induced strong cellular responses and these responses could be enhanced when the vaccine was used with an adjuvant. Li and colleagues have tested whether porcine CD40 ligand (CD40L) and granulocyte-macrophage colony-stimulating factor (GMCSF) have positive immunostimulatory effects on vaccines against porcine circovirus-associated disease. Their data show that CD40L and GMCSF enhanced the cellular immune responses and protective efficacy of the vaccines. They argue that these adjuvants could be used in vaccines against porcine circovirus. Finally, Shobia et al. have studied the mechanism by which Carica papaya leaf extracts enhance platelet counts in individuals infected with Dengue virus. Their data indicate that the extracts interact with platelets, suggesting a direct mechanism of action.

I would like to thank all of the authors and reviewers for their contributions to this issue of Viral Immunology.