An Update on HIV

The current issue of Viral Immunology features two comprehensive reviews on human immunodeficiency virus (HIV), a causative agent of acquired immune deficiency syndrome. It is now clear that HIV-infected individuals treated with antiretroviral therapy (ART) live as long as uninfected individuals. Nevertheless, ART is not risk-free because of issues associated with drug toxicity, drug resistance, and drug–drug interactions. In the first review, Sharilyn Almodovar discusses the complexity of HIV persistence and pathogenesis in the lung during ART, particularly in the context of chronic obstructive pulmonary disease, pulmonary arterial hypertension, and lung cancer. Several aspects of the complexity of HIV persistence and challenges with ART are discussed, as well as suggestions for new avenues of research. In the second review, Rametse and colleagues discuss the role of semen in the balance between inflammation and tolerance in the female genital tract and specifically ask whether it contributes to HIV risk. Since the natural inflammatory response to semen deposited in the female genital tract may result in recruitment of activated HIV target cells into the female genital mucosa, the authors focus on the constituents of semen that may increase the risk for HIV infection in women.

In addition to the two reviews, a research paper by Fu and colleagues investigates the possibility of using small interfering RNA against KIR3DL1 (an inhibitory receptor on natural killer [NK] cells) as a potential gene therapeutic agent in controlling HIV-1 infection. The data indicate that this treatment enhances the ability of the NK cells to kill HIV-1–infected cells in vitro, suggesting that it may be a viable therapeutic agent for HIV-1 infected people.

Two papers in this issue focus on influenza. Vogel and colleagues point out that infection with influenza A virus (IAV) leads to acute lung injury and sometimes fatal complications, especially in immunocompromised, elderly, or chronically infected individuals. By analyzing the impact of the infecting dose of IAV in a mouse model, they demonstrate that early cytokine dysregulation is a feature of high-dose infections and is characterized by significantly elevated levels of interferon-α, tumor necrosis factor-α, chemokine (C-X-C motif) ligand 9, interleukein-6, and monocyte chemoattractant protein-1 within the first 2 days. The authors speculate that early cytokine dysregulation coupled with viral replication plays a role in pulmonary damage and high mortality in lethally infected mice. These early and excessive cytokine responses may be a key aspect of pandemic strains of IAV. Therefore, considerable efforts have been directed at developing universal vaccines against circulating and future strains of the virus. In this regard, Lohia and Baranwal used an immunoinformatics approach to identify conserved CD4+ and CD8+ T-cell epitopes in both seasonal and pandemic strains of IAV. The authors identify several broadly active peptides that induced potent immune responses in a diverse group of individuals.

Hepatitis virus infections are a major clinical problem in the world today because they can cause chronic hepatitis, cirrhosis, and, in some cases, hepatocellular carcinoma. In the case of hepatitis B virus, the major shortcoming of current nucleotide analogue therapies is that the virus can rebound if the therapy is stopped. Chokshi and colleagues investigated the host immune profiles associated with rebound versus stable control of the virus. Their data indicate that the analysis of serum cytokine levels in concert with virologic and clinical parameters may help to identify patients who can successfully discontinue antiviral therapy. In a similar approach, Idrees and associates have analyzed the expression of human immune responsive genes (MMP-9, OAS1) and the fibrogenic responsive gene (KRT19) in patients with chronic hepatitis C virus infection. Their data suggest that noninvasive gene analysis approaches can be used to determine the levels of liver fibrosis and potentially offer useful information on hepatitis C virus pathogenesis in general. The hope is that analytic approaches such as these will lead to better therapeutic regimens against hepatitis viruses.

Finally, Freitas de Oliveira and colleagues investigated the putative association of polymorphisms in the DC-SIGN (CD209) gene with Dengue virus infection and its pathogenesis in residents from the state of Para, Brazil. The authors detected a protective role of the gene in regulating the spectrum of symptoms during the early acute phase of Dengue virus infection, and possibly also influencing the level of viremia.

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