Abstract
Two articles in the issue focus on innate immunity to two emerging viruses that pose a significant clinical threat. Evans and colleagues investigate immune evasion mechanisms by WNV, a human pathogen that can cause symptomatic infections associated with meningitis and encephalitis. The authors show that WNV infection promotes degradation of the interferon (IFN) receptor subunit 1 and thereby impairs the host IFN response. Chaaitanya and colleagues have investigated the role of proinflammatory cytokines and chemokines in chronic arthropathy in CHIKV infection. CHIKV causes mild to severe febrile illness and can sometimes elicit long-lasting polyarthritis. The pattern of cytokines and chemokines that were elevated during chronic infection were characteristic of arthritic diseases, suggesting that arthritic intervention strategies should also be considered for chronic CHIKV arthritis.
Several papers in the current issue address the adaptive immune response to a wide variety of viruses. A particularly significant group of viruses are the herpesviruses, which mediate an acute infection, followed by the establishment of lifelong latency. Tsai and associates have examined the roles of IFN-γ and perforin in the control of acute or reactivated murine γ-HV infection. Using gene knockout mice, the authors show differential roles for these key effector molecules depending on the host strain of mice. These strain differences were also reflected in the efficacy of different immunotherapeutic strategies. The mechanisms that allow herpesviruses to evade host immunity over the long term are not well understood. Studies by Loewendorf and colleagues show that mouse CMV-specific memory T cells do not decrease in number after thymectomy, indicating that recent thymic emigrants are not required for their maintenance. Furthermore, persistent mouse CMV replication in the salivary gland did not significantly impact the T-cell memory compartment in latently infected animals. Unlike herpesviruses, HIV primarily persists by continual replication in the face of a robust and continuous host response. This eventually results in a collapse of the host response and the development of immunodeficiency. Highly active antiretroviral therapy (HAART) reduces viral loads, allowing for restoration of T-cell numbers in the periphery. However, its efficacy in restoring functional immunity is not fully elucidated. Nyakeriga and colleagues now show that HAART-mediated control of viral replication led to partial restoration of CD40L expression, and to increased IL-12 production in some patients that was related to viral loads.
TBEV is a Flavivirus that induces meningitis, encephalitis, or meningoencephalitis in infected individuals and occasionally results in death. The factors associated with mortality following TBEV infection are not known. Using a mouse model of TBEV infection, Fujii and co-workers show that infection severity impacts the antigen specificity of the T-cell response, but not the number or activation status of brain-infiltrating T cells. In a related article, Bhullar and colleagues have developed a sensitive enzyme-linked immunosorbent assay protocol for HSV antigen detection in cerebrospinal fluid. The assay exhibits good sensitivity and specificity in both cerebrospinal fluid and sera, and will be useful for the diagnosis of herpes simplex encephalitis. The involvement of different T-cell subsets in the control of HBV infection is addressed by Zhai and colleagues. The authors examined blood samples from 30 patients with HBV-associated acute-on-chronic liver failure (ACLF), 30 patients with chronic hepatitis B, and 30 normal controls. Interestingly, the ratio of Th-17 to regulatory T cells (Treg) was inversely associated with the survival of ACLF patients, suggesting that Th-17 to Treg ratios may be a prognostic marker for the disease. Treg also play a role in HIV and tuberculosis co-infections. This issue is highlighted by a patient case study that is presented by Sued and colleagues.
On the vaccine front, Wiesener and colleagues present an analysis of the protective efficacy of different DNA plasmid-based influenza vaccines in a mouse model of experimental influenza A virus infection. The highest protective efficacy was observed following vaccination with plasmids expressing hemagglutinin (HA) and neuraminidase (NA), as well as a mixture of plasmids encoding a mix of several viral proteins. However, intramuscular application of the HA/NA mix was the most efficient procedure to decrease virus replication and to prevent immunopathology in lung tissue of influenza A virus-infected mice. Along similar lines, Tang and colleagues have developed a baculovirus system to produce influenza virus-like particles (VLP) that express influenza HA, NA, and matrix proteins. Mice vaccinated with VLP were protected from death following infection with a high-dose (normally lethal) influenza virus challenge. The advantage of this system is that the VLP are easy to purify and can be produced in large quantities. Along the same lines, Ferrer and colleagues show that a recombinant MVA vector expressing the secreted version of BoHV-1 glycoprotein D can induce systemic and mucosal immunity in mouse and rabbit models.