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Introduction As a homologue of the angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2) has been identified as the main receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion. We aimed to investigate the role of serum ACE in predicting the coronavirus disease 2019 (COVID-19) disease progression and the underlying mechanisms. Methods We retrospectively enrolled 120 patients with confirmed COVID-19 who underwent serum ACE detection on admission. The clinical characteristics and laboratory findings during hospitalization were evaluated dynamically to identify the potential risk factors for disease progression. Results ACE level was demonstrated as one of the independent risk factors. Patients with ACE level ≤ 33.5 U/L showed a higher cumulative virus RNA detection rate, elevated pro-inflammatory mediators levels, declined lymphocyte count, and decreased SARS-CoV-2-specific antibodies than those with ACE level > 33.5 U/L. Conclusion Lower serum ACE levels in relation to delayed virus elimination, hyperinflammatory condition, and impaired host antiviral immune responses contribute to disease progression of COVID-19.

The RNA interference (RNAi) pathway directs an important antiviral immunity mechanism in plants and invertebrates. Recently, we and others have demonstrated that the antiviral RNAi response is also conserved in mammals, at least to five distinct RNA viruses, including Zika virus (ZIKV). ZIKV may preferentially infect neuronal progenitor cells (NPCs) in the developing foetal brain. Ex vivo ZIKV infection induces RNAi-mediated antiviral response in human NPCs, but not in the more differentiated NPCs or somatic cells. However, litter is known about the in vivo property or function of the virus-derived small-interfering RNAs (vsiRNAs) targeting ZIKV. Here we report a surprising observation: different from ex vivo observations, viral small RNAs (vsRNAs) targeting ZIKV were produced in vivo upon infection in both central neuron system (CNS) and muscle tissues. In addition, our findings demonstrate the production of canonical vsiRNAs in murine CNS upon antiviral RNAi activation by Sindbis virus (SINV), suggesting the possibility of antiviral immune strategy applied by mammals in the CNS.

Duck hepatitis A virus 1 (DHAV-1) infection in mature ducks has previously been proposed as a small-animal model for human hepatitis A. However, basic research on the outcome of DHAV-1 infection in mature ducks is limited. Here, we examined the course of viremia, the characteristics of antibody responses, and the profiles of plasma cytokines in mature ducks infected with DHAV-1. During the course of infection, the viremia was detectable soon after infection and persisted for 196 days, however, the ducks presented as clinically asymptomatic. Specific and timely immunoglobulin G (IgG), IgM, and IgA1 responses were elicited. At the same time, extensive inhibition of viral replication was observed with increasing IgG concentration. With respect to pattern-recognition receptors, TLR-7 was mainly involved in triggering the innate defense against the DHAV-1 infection. In addition, plasma immune analytes were measured and were determined to have bidirectional roles in virus clearance. It was concluded that DHAV-1 spreads quickly in blood. The spontaneous clearance of DHAV-1 during asymptomatic infection in mature ducks depends on the cooperation of timely antibody responses and alert innate immune responses. Moreover, the delayed clearance may be associated with a weak interferon-γ-producing CD8+ T cell response. This study allows us to reveal the mechanism of clearance and persistence of DHAV-1 infection in mature ducks. We anticipate that it will provide a basis for future studies focused on defining the nature mechanisms involved in the clearance and persistence of human hepatitis virus.

Infectious bursal disease (IBD) is a highly contagious disease of chickens which leads to immunosuppression. In our previous study it was demonstrated that, possibly, CD4(+) and CD8(+) T cells may employ perforin and granzyme-A pathway for the clearance of IBDV-infected bursal cells. In this study, we evaluated the cytotoxic T cell responses involving two independently functioning but complementary mechanisms: Fas-Fas ligand and perforin-granzyme pathways in IBDV-infected chickens. As demonstrated previously, infection of chickens with IBDV was accompanied by influx of CD8(+) T cells in the bursa and spleen. There was an upregulation in the gene expression of cytolytic molecules: Fas and Fas ligand (FasL), perforin (PFN) and granzyme-A (Gzm-A) in bursal and in the splenic tissues of IBDV inoculated chickens. Additionally, for the first time, we detected Fas, Fas ligand, Caspase-3 and PFN producing CD8(+) T cells in the bursa and spleen of IBDV-infected chickens. The infiltration and activation of CD8(+) T cells was substantiated by the detection of Th1 cytokine, IFN-γ. These data suggest that T cells may be involved in the clearance of virus from the target organ bursa and peripheral tissues such as spleen. The findings of these studies provide new insights into the pathogenesis of IBD and provide mechanistic evidence that the cytotoxic T cells may act through both Fas-FasL and perforin-granzyme pathways in mediating the clearance of virus-infected cells.

Background Epidemiologic evidence links tobacco smoke and increased risk for influenza in humans, but the specific host defense pathways involved are unclear. Objective We developed a model to examine influenza-induced innate immune responses in humans and test the hypothesis that exposure to cigarette smoke alters nasal inflammatory and antiviral responses to live attenuated influenza virus (LAIV). Methods This was an observational cohort study comparing nasal mucosal responses to LAIV among young adult active smokers (n = 17), nonsmokers exposed to secondhand smoke (SHS; n = 20), and unexposed controls (n = 23). Virus RNA and inflammatory factors were measured in nasal lavage fluids (NLF) serially after LAIV inoculation. For key end points, peak and total (area under curve) responses were compared among groups. Results Compared with controls, NLF interleukin-6 (IL-6) responses to LAIV (peak and total) were suppressed in smokers. Virus RNA in NLF cells was significantly increased in smokers, as were interferon-inducible protein 10:virus ratios. Responses in SHS-exposed subjects were generally intermediate between controls and smokers. We observed significant associations between urine cotinine and NLF IL-6 responses (negative correlation) or virus RNA in NLF cells (positive correlation) for all subjects combined. Conclusions Nasal inoculation with LAIV results in measurable inflammatory and antiviral responses in human volunteers, thus providing a model for investigating environmental effects on influenza infections in humans. Exposure to cigarette smoke was associated with suppression of specific nasal inflammatory and antiviral responses, as well as increased virus quantity, after nasal inoculation with LAIV. These data suggest mechanisms for increased susceptibility to influenza infection among persons exposed to tobacco smoke.

Introduction and aim. Hepatitis C virus (HCV) infection is a global medical problem. HLA –DRB1 alleles have an important role in immune response against HCV. The aim of this study is to clarify the contribution of HLA –DRB1 alleles in HCV susceptibility in a multicentre family-based study. Material and methods. A total of 162 Egyptian families were recruited in this study with a total of 951 individuals (255 with chronic hepatitis C (CHC), 588 persons in the control group(-ve household contact to HCV) and 108 persons who spontaneously cleared the virus (SVC). All subjects were genotyped for HLA -DRB1 alleles by SSP-PCR and sequence based typing (SBT) methods. Results. The carriage of alleles 3:01:01 and 13:01:01 were highly significant in CHC when compared to that of control and SVC groups [OR of 3 family = 5.1289, PC (Bonferroni correction ) = 0.0002 and 5.9847, PC = 0.0001 and OR of 13 family = 4.6860, PC = 0.0002 and OR = 6.5987, PC = 0.0001 respectively]. While DRB1*040501, DRB1*040101, DRB1*7:01:01 and DRB1*110101 alleles were more frequent in SVC group than CHC patients (OR = 0.4052, PC = 0.03, OR: OR = 0.0916, PC = 0.0006, OR = 0.1833, PC = 0.0006 and OR = 0.4061, PC = 0.0001 respectively). Conclusions. It was concluded that among the Egyptian families, HLA- DRB1*030101, and DRB1*130101 alleles associated with the risk of progression to CHC infection, while DRB1*040101, DRB1*040501, DRB1*7:01:01and DRB1*110101 act as protective alleles against HCV infection.

The severe acute respiratory syndrome (SARS) epidemic started in late 2002 and swiftly spread across 5 continents with a mortality rate of around 10%. Although the epidemic was eventually controlled through the implementation of strict quarantine measures, there continues a need to investigate the SARS coronavirus (SARS-CoV) and develop interventions should it re-emerge. Numerous studies have shown that neutralizing antibodies against the virus can be found in patients infected with SARS-CoV within days upon the onset of illness and lasting up to several months. In contrast, there is little data on the kinetics of T cell responses during SARS-CoV infection and little is known about their role in the recovery process. However, recent studies in mice suggest the importance of T cells in viral clearance during SARS-CoV infection. Moreover, a growing number of studies have investigated the memory T cell responses in recovered SARS patients. This review covers the available literature on the emerging importance of T cell responses in SARS-CoV infection, particularly on the mapping of cytotoxic T lymphocyte (CTL) epitopes, longevity, polyfunctionality and human leukocyte antigen (HLA) association as well as their potential implications on treatment and vaccine development.