Complications of HIV Infection

The development of effective antiretroviral therapy has turned human immunodeficiency virus (HIV) infection from a death sentence into a manageable chronic disease. Nonetheless, HIV-infected individuals can face long-term complications. In the current issue of Viral Immunology, Almodovar and colleagues note that one serious and potentially life-threatening complication of HIV infection is pulmonary arterial hypertension (PAH). PAH is characterized by high pulmonary artery pressures, inflammation, pulmonary vascular remodeling, increased circulating inflammatory cytokines, and the presence of cells that obliterate the lumina of pulmonary arteries and form plexiform lesions. Although PAH is rare in the general population, it afflicts HIV-infected individuals at relatively high frequencies (1 in 200) regardless of their antiretroviral drug status, HIV viral load, CD4 T cell counts, or duration of HIV infection. To further investigate the pathology of this disease, the Almodovar research team has investigated disease progression in the lungs of juvenile simian HIV-nef-infected macaques. They report that infected macaques with simian HIV-nef developed pulmonary vascular lesions and expressed a gene program characteristic of pathologic cardiac hypertrophy frequently seen in the hearts of patients with PAH. Furthermore, their studies revealed alterations in cytokine expression consistent with other forms of PAH, highlighting the utility of this model to dissect the underlying pathogenic mechanisms.

Two articles in this issue of Viral Immunology focus on different aspects of the innate immune response to viral infection. Vargas-Castillo et al. have genotyped single nucleotide polymorphisms located in immune response-related genes in patients with dengue fever, dengue hemorrhagic fever, and healthy donors from an endemic region in Mexico. Their data indicate that allelic variations in immune response genes can play an important role in the development of hemorrhagic fever, but that the genetic background may modify the role of immune response genes leading to the milder illness often observed in Mexican population. Trujillo-Ochoa and colleagues note that bilirubin, a metabolite with increased concentrations in plasma during viral hepatitis, is a potential immune modulator, but the underlying mechanisms are unclear. Here, they report that conjugated bilirubin might affect regulatory T cell activity through a TIM-3-mediated mechanism, ultimately leading to an anti-inflammatory hepatoprotective effect.

The rapid and accurate diagnosis of viral pathogens is essential for the prevention and management of infectious viral diseases. Consequently, the development and testing of assays are important aspects of both public and animal health control. In this regard, Athanasiou and colleagues have evaluated assays for the detection of canine distemper virus (CDV). The authors compared the diagnostic performance of a direct immunofluorescent assay and an established polymerase chain reaction detection assay used as a gold standard for CDV diagnosis. Their data indicated that the immunofluorescent assay was specific and adequately sensitive for the detection of CDV antigen. Zhou et al. report on the development of competitive enzyme-linked immunosorbent assays for bluetongue virus (BTV). The assay is based on monoclonal antibodies developed by the authors that are specific for the VP2 protein of BTV. These new assays will be invaluable for the diagnosis and epidemiological studies of BTV infections.

The most effective public health or veterinary approach for controlling viral infections is the development and introduction of effective and safe vaccines. In the case of rotavirus infections, the two currently approved live attenuated vaccines “RotaTeq” and “Rotarix” are associated with occasional safety problems. In an attempt to develop an improved vaccine, Afchangi et al. take advantage of the fact that the viral NSP4 protein exhibits natural adjuvant properties. They created and tested a rotavirus NSP4-VP6 fusion protein vaccine in a mouse model. The authors show that immunization with NSP4-VP6 elicited stronger responses than VP6 alone, suggesting that this strategy may lead to the development of an improved rotavirus vaccine. In another study, Miao et al. compare two different rabies virus immunization strategies (Essen and Zagreb Regimens) in a double-blind, randomized clinical trial. Their data show that both regimens led to complete seroconversion, but the Essen regimen induced a superior neutralizing antibody response. These findings are important for clinicians' application of rabies vaccine immunization programs.

One final article in this issue of Viral Immunology addresses hepatitis C virus (HCV), which poses an important global health issue. Direct antiviral therapy against chronic HCV infection has proven to be very effective. Aziz et al. report new data on the overall efficacy of Sofosbuvir therapy and show that the drug did not induce viral resistance in their studies.

I would like to thank all of the authors for their excellent contributions to the Journal and all of the reviewers for their efforts in maintaining the high quality of published articles.