Both respiratory syncytial virus (RSV) and influenza A virus (IAV) may infect human peripheral blood mononuclear leukocytes (PBMC) during the immune response to viral challenge as the cells are recruited to the respiratory tract. The current studies demonstrated differences in PBMC responses to the two viruses very early after exposure, including reduced fos protein and CD69 expression and IL-2 production by RSV-exposed T lymphocytes. Exposure to RSV resulted in reduced lymphocyte proliferation despite evidence of a virus-specific T lymphocyte frequency equivalent to that for influenza virus. Reduced RSV-induced proliferation was not due to apoptosis, which was itself reduced relative to that of influenza virus-exposed T lymphocytes. The data indicate that differential immune responses to RSV and influenza virus are determined early after exposure of human PBMC and support the concept that the anamnestic immune response that might prevent clinically evident reinfection is attenuated very soon after exposure to RSV. Thus, candidate RSV vaccines should be expected to reduce but not prevent clinical illness upon subsequent infection by RSV. Furthermore, effective therapeutic agents for RSV are likely to be needed, especially for high-risk populations, even after vaccine development.

Interleukin-6⁻¹⁷⁴ (IL-6⁻¹⁷⁴) and tumor necrosis factor α⁻³⁰⁸ (TNFα⁻³⁰⁸) are high-cytokine-producing genotypes that are known to increase the susceptibility to infectious diseases, but their influence on cytokine production induced by respiratory viruses is unknown. We exposed human monocyte-derived macrophages from IL-6⁻¹⁷⁴, TNFα⁻³⁰⁸, and normal genotype donors to different respiratory viruses. Respiratory syncytial virus (RSV) stimulation was associated with higher IL-6 concentrations in IL-6⁻¹⁷⁴ donors than in normal donors (P = 0.015); 2 of 7 (29%) polymorphic donors were poor responders compared with 6 of 7 (86%) normal donors (P = 0.002). Adenovirus, influenza virus, and RSV stimulations were associated with higher TNFα concentrations in TNFα⁻³⁰⁸ donors than in normal donors (P = 0.03, <0.01, <0.01). A similar trend was seen with rhinovirus stimulation, but this was not significant. These results show that IL-6⁻¹⁷⁴ and TNFα⁻³⁰⁸ gene polymorphisms lead to enhanced production of the respective cytokines when exposed to specific respiratory viruses. This, in turn, may influence the susceptibility to, severity of, and recovery from respiratory virus infections, or influence the immune response to and reactogenicity of viral vaccines.

Background Heterozygosity at HLA class I loci is generally considered beneficial for host defense. We report here an element of HLA class I homozygosity that may or may not help preserve its existence in populations but which could indicate a new avenue for antiviral research. Methods Lymphocytes from serologically HLA-homozygous or -heterozygous donors were examined for synthesis of influenza virus proteins and RNA after exposure to virus as peripheral blood mononuclear cells. The virus-exposed lymphocytes were also examined for internalization of the virus after exposure, and for susceptibility to virus-specific cytotoxic T lymphocytes in comparison with virus-exposed monocytes/macrophages and unseparated peripheral blood mononuclear cells. Results were compared using two-tailed Fisher’s exact test. Results Serologically-defined HLA-A2-homozygous lymphocytes, in contrast to heterozygous lymphocytes, did not synthesize detectable influenza virus RNA or protein after exposure to the virus. HLA-A2-homozygous lymphocytes, including both homozygous and heterozygous donors by genetic sequence subtyping, did internalize infectious virus but were not susceptible to lysis by autologous virus-specific cytotoxic T lymphocytes (“fratricide”). Similar intrinsic resistance to influenza virus infection was observed with HLA-A1- and HLA-A11-homozygous lymphocytes and with HLA-B-homozygous lymphocytes. Conclusions A significant proportion of individuals within a population that is characterized by common expression of HLA class I alleles may possess lymphocytes that are not susceptible to influenza virus infection and thus to mutual virus-specific lysis. Further study may identify new approaches to limit influenza virus infection.

We report the generation of murine triomas by fusing splenocytes from mice previously immunized with HBsAg ay-subtype and a hybridoma, secreting anti-HBsAg ad-subtype monoclonal antibody, which was rendered HGPRT- by induced mutagenesis with N-methyl-N'nitro-N-nitrosoguanidine. The fusion yielded a 83.8% of hybrids showing the antigen specificity of the parental hybridoma and a 16.1% of bi-specific monoclonal antibodies. One of them, coded as 1C8A5, showing a heavy chain isotype (IgG1/IgG2b) was used as capture reagent in an ultramicro-ELISA. As little as 0.78 I.U. of both HBsAg ad- and ay-subtypes could be realiably detected.