Immune response to influenza A(H1N1)v in HIV-infected patients.

INTRODUCTION: HIV infection is considered a risk factor for severe outcomes of influenza A(H1N1)v infection. However, data on immune response against influenza A(H1N1)v virus in HIV-infected patients are lacking. METHODOLOGY: Data from seven HIV-positive and 14 HIV-negative patients infected with A(H1N1)v and from 23 HIV-positive and six HIV-negative asymptomatic controls were analyzed to evaluate the clinical picture, A(H1N1)v viral shedding, and the immune response against the virus. RESULTS: Patients displayed mainly upper respiratory tract diseases (57.1%), while pneumonia was diagnosed only in HIV-negative patients (23.8% of subjects, of which 4.8% required intensive care unit admission). At day seven, 29% of HIV-infected patients were still positive for A(H1N1)v by RT-PCR on nasopharyngeal swabs. Interestingly, a persistence of CXCL10 secretion at high level and lower IL-6 levels was observed in HIV-positive subjects. The geometric mean haemagglutination inhibition titer (HI-GMT) and anti-influenza IgM levels were lower in HIV-positive individuals while anti-influenza IgG levels remained similar in the two groups. CONCLUSIONS: The immune impairment due to HIV infection could affect A(H1N1)v clearance and could lead to a lower antibody response and a persistent secretion of CXCL10 at high levels. However, the lower IL-6 secretion and treatment with highly active antiretroviral therapy (HAART) could result in a milder clinical picture.

Influenza monitoring in Sardinia, Italy identifies H3 subtype in Mediterranean wild migratory birds.

INTRODUCTION: Wild migratory birds are global distributors of pathogens. Sardinia, Italy, is the second largest Island in the Mediterranean and is a land bridge between Europe and Africa. METHODOLOGY: We designed a surveillance protocol to investigate wild migratory birds for presence, frequency, and type of avian influenza viruses. We collected over 4,000 avian samples and compared three sampling methods, fecal, cloacal, and tracheal, to determine the most productive for virus identification. To determine frequency of infection, RNA was extracted and RT-PCRs for avian influenza virus genes were run. Positive samples were cultivated for live virus, sub typed and sequenced. RESULTS: Forty-four samples were positive for influenza nucleoprotein gene. We identified two previously unidentified H3 subtype strains and found cloacae to have the highest rate of virus identification and fecal sampling to provide quality RNA and repeatable results for determination of virus presence. CONCLUSION: Our investigation provides information on the frequency of Mediterranean avian influenza viruses, and validates the initiation of an avian influenza surveillance protocol.  Taken together with global avian influenza findings, these results give insight into infectious disease distributions which is important for viral pandemic monitoring and design of preventative measures.

Interleukin-6 is a potential biomarker for severe pandemic H1N1 influenza A infection.

Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.

Loss of Roquin induces early death and immune deregulation but not autoimmunity.

The substitution of one amino acid in the Roquin protein by the sanroque mutation induces a dramatic autoimmune syndrome in mice. This is believed to occur through ectopic expression of inducible T cell co-stimulator (ICOS) and unrestrained differentiation of follicular T helper cells, which induce spontaneous germinal center reactions to self-antigens. In this study, we demonstrate that tissue-specific ablation of Roquin in T or B cells, in the entire hematopoietic system, or in epithelial cells of transplanted thymi did not cause autoimmunity. Loss of Roquin induced elevated expression of ICOS through T cell-intrinsic and -extrinsic mechanisms, which itself was not sufficient to break self-tolerance. Instead, ablation of Roquin in the hematopoietic system caused defined changes in immune homeostasis, including the expansion of macrophages, eosinophils, and T cell subsets, most dramatically CD8 effector-like T cells, through cell-autonomous and nonautonomous mechanisms. Germline Roquin deficiency led to perinatal lethality, which was partially rescued on the genetic background of an outbred strain. However, not even complete absence of Roquin resulted in overt self-reactivity, suggesting that the sanroque mutation induces autoimmunity through an as yet unknown mechanism.

Immune response to influenza A (H1N1)v monovalent MF59-adjuvanted vaccine in HIV-infected patients.

Immunogenicity of influenza A (H1N1)v MF59-adjuvanted vaccine was studied in HIV-infected patients. The vaccine was effective in inducing a protective immune response in patients with a CD4 >200 cells/µL while individuals with CD4 <200 cells/µL showed lower rates of seroconversion and seroprotection. These results underscore the usefulness of immunization against influenza in HIV-infected patients, though a boosting dose of vaccine may be required in seriously immunocompromised patients.