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Recent studies have documented prolonged expression of viral antigens and RNA and associated inflammation after infection with SARS-CoV-2 in a substantial proportion of infected patients. The persisting SARS-CoV-2 effects and findings, with inflammation associated with continued detection of viral antigens, especially resemble those previously reported for influenza virus, as well as respiratory syncytial virus (RSV). The reports indicate the need for improved insight into the mechanisms whereby post-SARS-CoV-2 infection-related illness is apparently more common and perhaps even more persistent after infection than observed for other respiratory viruses. [ABSTRACT FROM AUTHOR]

In the pathogenesis of influenza virus infection, lymphocyte apoptosis as a part of the infection and/or the immune response to the virus can be somewhat puzzling. The percentage of human T lymphocytes within the peripheral blood mononuclear cell population that becomes apoptotic greatly exceeds the percentage that are infected after exposure to the virus, consistent with substantial apoptosis of bystander T lymphocytes. Studies reveal an important role of viral neuraminidase expression by co-cultured monocyte/macrophages in induction of apoptosis, including that of uninfected bystander lymphocytes. Despite these observations, it is a reasonable perspective to recognize that the development of lymphocyte apoptosis during the response to infection does not preclude a successful immune response and recovery of the infected host in the great majority of cases. Further investigation is clearly warranted to understand its role in the pathogenesis of influenza virus infection for human subjects. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus infections recur throughout life despite induction of immunity by the first natural infection. An effective vaccine has long been sought but no vaccine is currently licensed, although promising candidates are currently being developed based on greater knowledge of the virus properties. However, there are significant populations that may not be protected adequately by a vaccine or are unable to be vaccinated. Thus, there is a continued need for effective therapeutic agents to treat the infection, especially in higher-risk individuals, a perspective presented in this article. [ABSTRACT FROM AUTHOR]

The H2N2 virus that was identified was found to be similar to H2N2 viruses that circulated in humans in 1957-1958 at the beginning of the so-called "Asian" influenza pandemic. Influenza A virus (IAV) is a major cause of respiratory infections worldwide, with the most severe cases occurring in the very young and in elderly individuals [[1]]. Unlike the seasonal IAV age risks noted above, pandemic IAV infections often disproportionately kill young adults, as has been well documented for the 1918 [[1], [5]], 1968 [[6]], and even the 2009 [[7], [9]] pandemics. Seasonal IAV was responsible for an average of 12,000-52,000 deaths annually between 2010 and 2020 in the U.S. before the onset of the COVID-19 pandemic, according to the Centers for Disease Control and Prevention, with preventive measures addressing the latter respiratory infection also reducing the impact of seasonal influenza. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

The current studies were undertaken to determine the susceptibility of human alveolar macrophages (AMs) to influenza A virus (IAV) infection in comparison with autologous peripheral blood-derived monocytes-macrophages (PBMs). AMs and PBMs were exposed to IAV in vitro and examined for their ability to bind and internalize IAV, and synthesize viral proteins and RNA. PBMs but not AMs demonstrated binding and internalization of the virus, synthesizing viral proteins and RNA. Exposure of AMs in the presence of a sialidase inhibitor or anti-IAV antibody resulted in viral protein synthesis by the cells. Exposure of AMs to fluorescein isothiocyanate-labeled IAV in the presence of anti-fluorescein isothiocyanate antibody also resulted in viral protein synthesis. Thus, human AMs are apparently not susceptible to direct infection by a human IAV but are likely to be infected indirectly in the setting of exposure in the presence of antibody that binds the challenging strain of IAV. [ABSTRACT FROM AUTHOR]

Examines the effects of nitrogen dioxide exposure on airway inflammation and blood cells. Identification of a dose-related decrease in hematocrit; Decrease in circulating total lymphocytes and T lymphocytes; Gender difference in the response of blood lymphocytes CD4 to nitrogen dioxide exposure.

Nitrogen dioxide (NO2) exposure has been linked with increased respiratory illness and infection. The objective of this study was to determine whether exposure at peak indoor levels causes airway inflammation or impairs local or systemic host defense in humans either immediately or 18 h after exposure. In an initial phase, 12 volunteers were exposed to purified air or a targeted concentration of 2.0 ppm NO2 for 6 h, with intermittent exercise, and underwent bronchoalveolar lavage (BAL) 18 h after exposure. In a second phase, 12 volunteers participated in an identical exposure protocol but BAL was performed immediately after exposure. Eighteen hours after exposure to NO2, polymorphonuclear leukocytes recovered by BAL increased from 2.2 +/- 0.3 to 3.1 +/- 0.4% (p = .005) and small decreases were found in the percentage of blood CD8+ T lymphocytes ( p = .01) and in blood T lymphocytes expressing neither CD4 nor CD8 (p = .03). These variables were not significantly different immediately after NO2 exposure. Nitrogen dioxide exposure did not alter lymphocyte subsets in BAL or alveolar macrophage function at either time point. Exposure to 2.0 ppm NO2 for 6 h with exercise causes airway inflammation and may alter blood lymphocyte populations 18 h after exposure. [ABSTRACT FROM AUTHOR]

Study Objective: To determine the efficacy and toxicity of intralesionally administered interferons in the treatment of condyloma acuminatum.Design: Randomized, double-blind, and placebo-controlled study.Setting: Outpatient clinics at university medical centers.Patients: Seventy-nine patients with biopsy-proved condyloma acuminatum that was refractory to conventional therapy were enrolled in the study.Interventions: Alpha-2b, alpha-nl-, and beta-interferons were used. One wart on each patients was injected three times per week for 4 weeks with either 1 x 10(6) units of interferon or placebo.Measurements and Main Results: Forty-seven percent of warts injected with interferon resolved completely, compared with 22% of placebo-injected warts (P = 0.009). In addition, more recipients of interferon had a complete resolution of uninjected lesions. No differences in rates of response were noted among the different interferon groups. Approximately one third of interferon-injected warts recurred, compared with none of four placebo-injected warts. Intralesionally administered interferon was nontoxic and well tolerated, although transient pain on injection was observed frequently.Conclusions: Intralesional administration of each of these three interferons appears to be useful in treating condyloma acuminatum. However, the frequent recurrence of disease and the failure of many lesions to resolve indicate that different regimens, such as longer courses of therapy or different routes of administration, should be evaluated to maximize beneficial effects of interferon for treating this common sexually transmitted disease. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a common cause of respiratory tract infections in infants and the elderly. Like many other pH-independent enveloped viruses, RSV is thought to enter at the cell surface, independently of common endocytic pathways. We have used a targeted small interfering RNA (siRNA) library to identify key cellular genes involved in cytoskeletal dynamics and endosome trafficking that are important for RSV infection. Surprisingly, RSV infection was potently inhibited by siRNAs targeting genes associated with clathrin-mediated endocytosis, including clathrin light chain. The important role of clathrin-mediated endocytosis was confirmed by the expression of well-characterized dominant-negative mutants of genes in this pathway and by using the clathrin endocytosis inhibitor chlorpromazine. We conclude that, while RSV may be competent to enter at the cell surface, clathrin function and endocytosis are a necessary and important part of a productive RSV infection, even though infection is strictly independent of pH. These findings raise the possibility that other pH-independent viruses may share a similar dependence on endocytosis for infection and provide a new potential avenue for treatment of infection. [ABSTRACT FROM AUTHOR]

Like many enveloped viruses, human respiratory syncytial virus (RSV) assembles at and buds from lipid rafts. Translocation of the envelope proteins to these membrane subdomains is essential for production of infectious virus, but the targeting mechanism is poorly understood and it is not known if other virus proteins are required. Here we demonstrate that F protein of RSV intrinsically targets to lipid rafts without a requirement for any other virus protein, including the SH and G envelope proteins. Recombinant virus deficient in SH and G but retaining F protein expression was used to demonstrate that F protein still localized in rafts in both A549 and HEp-2 cells. Expression of a recombinant F gene by use of plasmid vectors demonstrated that F contains its own targeting domain and localized to rafts in the absence of other virus proteins. The domain responsible for translocation was then mapped. Unlike most other virus envelope proteins, F is unusual since the target signal is not contained within the cytoplasmic domain nor did it involve fatty acid modified residues. Furthermore, exchange of the transmembrane domain with that of the vesicular stomatitis virus G protein, a nonraft protein, did not alter F protein raft localization. Taken together, these data suggest that domains present in the extracellular portion of the protein are responsible for lipid raft targeting of the RSV F protein. [ABSTRACT FROM AUTHOR]