RESUMEN
Experimental Zika virus infection in non-human primates results in acute viral load dynamics that can be well-described by mathematical models. The inoculum dose that would be received in a natural infection setting is likely lower than the experimental infections and how this difference affects the viral dynamics and immune response is unclear. Here we study a dataset of experimental infection of non-human primates with a range of doses of Zika virus. We develop new models of infection incorporating both an innate immune response and viral interference with that response. We find that such a model explains the data better than models with no interaction between virus and the immune response. We also find that larger inoculum doses lead to faster dynamics of infection, but approximately the same total amount of viral production.
Asunto(s)
Inmunidad Innata/inmunología , Interferencia Viral , Infección por el Virus Zika , Virus Zika , Animales , Biología Computacional , Interacciones Huésped-Patógeno/inmunología , Interacciones Huésped-Patógeno/fisiología , Macaca , Modelos Biológicos , Interferencia Viral/inmunología , Interferencia Viral/fisiología , Carga Viral/inmunología , Carga Viral/fisiología , Virus Zika/inmunología , Virus Zika/patogenicidad , Virus Zika/fisiología , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/virologíaRESUMEN
Antibodies play a crucial role in virus control. The production of antibodies requires virus-specific B cells to encounter viral antigens in lymph nodes, become activated, interact with different immune cells, proliferate and enter specific differentiation programmes. Each step occurs in distinct lymph node niches, requiring a coordinated migration of B cells between different subcompartments. The development of multiphoton intravital microscopy has enabled researchers to begin to elucidate the precise cellular and molecular events by which lymph nodes coordinate humoral responses. This Review discusses recent studies that clarify how viruses interfere with antibody responses, highlighting how these mechanisms relate to our topological and temporal understanding of B cell activation within secondary lymphoid organs.
Asunto(s)
Linfocitos B/virología , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/virología , Virosis/inmunología , Animales , Antígenos Virales/inmunología , Linfocitos B/inmunología , Linfocitos B/patología , Linfocitos T CD8-positivos/inmunología , Diferenciación Celular/inmunología , Humanos , Activación de Linfocitos/inmunología , Cooperación Linfocítica/inmunología , Modelos Inmunológicos , Linfocitos T Colaboradores-Inductores/inmunología , Interferencia Viral/inmunología , Virosis/patología , Virosis/virologíaAsunto(s)
Interferones/historia , Interferones/inmunología , Interferencia Viral/inmunología , Animales , Embrión de Pollo , Membrana Corioalantoides/inmunología , Membrana Corioalantoides/metabolismo , Membrana Corioalantoides/virología , Historia del Siglo XX , Calor , Virus de la Influenza A/inmunología , Interferones/metabolismoAsunto(s)
Interferones/historia , Interferones/inmunología , Interferencia Viral/inmunología , Animales , Embrión de Pollo , Membrana Corioalantoides/inmunología , Membrana Corioalantoides/metabolismo , Membrana Corioalantoides/virología , Historia del Siglo XX , Calor , Virus de la Influenza A/inmunología , Interferones/metabolismo , Virus de la Enfermedad de Newcastle/inmunología , Estabilidad Proteica , Virus Sendai/inmunología , Vaccinia/inmunologíaRESUMEN
BACKGROUND: Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. METHODS: Ferrets were first infected then challenged 1-14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. RESULTS: Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. CONCLUSIONS: The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season.
Asunto(s)
Modelos Animales de Enfermedad , Gripe Humana/inmunología , Gripe Humana/virología , Orthomyxoviridae/inmunología , Interferencia Viral/inmunología , Animales , Coinfección , Hurones , Humanos , Esparcimiento de VirusRESUMEN
Patients with HIV-1 and human T-lymphotropic virus type 2 (HTLV-2) coinfections often exhibit a clinical course similar to that seen in HIV-1-infected individuals who are long-term nonprogressors. These findings have been attributed in part to the ability of HTLV-2 to activate production of antiviral chemokines and to downregulate the CCR5 coreceptor on lymphocytes. To further investigate these observations, we tested the ability of recombinant Tax1 and Tax2 proteins to suppress HIV-1 viral replication in vitro. R5-tropic HIV-1 (NLAD8)-infected peripheral blood mononuclear cells (PBMCs) were treated daily with recombinant Tax1 and Tax2 proteins (dosage range 1-100 pM). Culture supernatants were collected at intervals from days 1 to 22 postinfection and assayed for levels of HIV-1 p24 antigen by ELISA. Treatment of PBMCs with Tax2 protein resulted in a significant reduction in HIV-1 p24 antigen levels (p<0.05) at days 10, 14, and 18 postinfection compared to HIV-1-infected or mock-treated PBMCs. This was preceded by the detection of increased levels of CC-chemokines MIP-1α/CCL3, MIP-1ß/CCL4, and RANTES/CCL5 on days 1-7 of infection. Similar, but less robust inhibition was observed in Tax1-treated PBMCs. These results support the contention that Tax1 and Tax2 play a role in generating antiviral responses against HIV-1 in vivo and in vitro.
Asunto(s)
Productos del Gen tax/fisiología , VIH-1/fisiología , Infecciones por HTLV-I/complicaciones , Quimiocinas CC/biosíntesis , Coinfección/inmunología , Coinfección/virología , Productos del Gen tax/inmunología , Proteína p24 del Núcleo del VIH/metabolismo , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/inmunología , Infecciones por HTLV-I/inmunología , Infecciones por HTLV-I/virología , Infecciones por HTLV-II/complicaciones , Infecciones por HTLV-II/inmunología , Infecciones por HTLV-II/virología , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Interferencia Viral/inmunología , Interferencia Viral/fisiología , Replicación Viral/inmunología , Replicación Viral/fisiologíaRESUMEN
Problem of poliomyelitis eradication is examined in the review. After the eradication of wild poliovirus, vaccine poliomyelitis virus continues to circulate in the human population. In rare cases it can cause the development of the disease. The authors describe disadvantages of the use of oral and inactivated poliomyelitis vaccines and note that by using oral poliomyelitis vaccine and eradication only of wild poliovirus, eradication of poliomyelitis as an infection will not succeed. As one of the approaches to reach this goal the authors propose the use of various enterovirus interference. Use of live enterovirus vaccine is described and its advantages and disadvantages are examined.
Asunto(s)
Brotes de Enfermedades/prevención & control , Enterovirus/inmunología , Poliomielitis/epidemiología , Poliomielitis/prevención & control , Poliovirus/inmunología , Vacunación/métodos , África/epidemiología , Asia/epidemiología , Erradicación de la Enfermedad/métodos , Humanos , Poliomielitis/inmunología , Poliovirus/patogenicidad , Vacuna Antipolio de Virus Inactivados/efectos adversos , Vacuna Antipolio de Virus Inactivados/inmunología , Vacuna Antipolio Oral/efectos adversos , Vacuna Antipolio Oral/inmunología , Interferencia Viral/inmunologíaRESUMEN
Competition and parasitism are two important selective forces that shape life-histories, migration rates and population dynamics. Recently, it has been shown in various pathosystems that parasites can modify intraspecific competition, thus generating an indirect cost of parasitism. Here, we investigated if this phenomenon was present in a plant-potyvirus system using two viruses of different virulence (Tobacco etch virus and Turnip mosaic virus). Moreover, we asked if parasitism interacted with the shade avoidance syndrome, the plant-specific phenotypic plasticity in response to intraspecific competition. Our results indicate that the modification of intraspecific competition by parasitism is not present in the Nicotiana benthamiana--potyvirus system and suggests that this phenomenon is not universal but depends on the peculiarities of each pathosystem. However, whereas the healthy N. benthamiana presented a clear shade avoidance syndrome, this phenotypic plasticity totally disappeared when the plants were infected with TEV and TuMV, very likely resulting in a fitness loss and being another form of indirect cost of parasitism. This result suggests that the suppression or the alteration of adaptive phenotypic plasticity might be a component of virulence that is often overlooked.
Asunto(s)
Adaptación Fisiológica , Nicotiana/virología , Virus de Plantas/fisiología , Adaptación Fisiológica/inmunología , Adaptación Fisiológica/fisiología , Interacciones Huésped-Patógeno/inmunología , Interacciones Huésped-Patógeno/fisiología , Modelos Biológicos , Fenotipo , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/virología , Virus de Plantas/inmunología , Virus de Plantas/patogenicidad , Potyvirus/inmunología , Potyvirus/patogenicidad , Potyvirus/fisiología , Nicotiana/crecimiento & desarrollo , Nicotiana/fisiología , Tobamovirus/inmunología , Tobamovirus/patogenicidad , Tobamovirus/fisiología , Interferencia Viral/inmunología , Interferencia Viral/fisiología , Virulencia/fisiologíaRESUMEN
A critical factor influencing the ability of the host to mount a robust immune response against a virus depends on the rapid recruitment of dendritic cells (DCs) presenting Ags. From the outset, this step sets the tempo for subsequent activation of virus-specific T cells. Despite this, how induction of the immune response might be modified by pathogens with the capacity to establish persistence is unclear. In this study, we have characterized the in vivo influence of murine gamma-herpesvirus K3-mediated interference with MHC class I in DCs that drive the initial adaptive immune response. We observed that gamma-herpesvirus could interfere with the very earliest phase of Ag presentation through K3 by directly targeting migratory and lymph node-resident DCs. These results show that a pathogen with the capacity to interfere with early Ag presentation can establish suboptimal conditions for rapid induction of the adaptive immune response and thus favor establishment of viral persistence.
Asunto(s)
Presentación de Antígeno/inmunología , Células Dendríticas/inmunología , Infecciones por Herpesviridae/inmunología , Rhadinovirus/inmunología , Infecciones Tumorales por Virus/inmunología , Animales , Enfermedad Crónica , Reactividad Cruzada/inmunología , Células Dendríticas/patología , Células Dendríticas/virología , Infecciones por Herpesviridae/metabolismo , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Rhadinovirus/patogenicidad , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/virología , Infecciones Tumorales por Virus/metabolismo , Interferencia Viral/inmunología , Proteínas Virales/antagonistas & inhibidores , Proteínas Virales/biosíntesisRESUMEN
Human metapneumoviruses (HMPVs) are recently identified Paramyxoviridae that contribute to respiratory tract infections in children. No effective treatments or vaccines are available. Successful defense against virus infection relies on early detection by germ line-encoded pattern recognition receptors and activation of cytokine and type I IFN genes. Recently, the RNA helicase retinoic acid-inducible gene I (RIG-I) has been shown to sense HMPV. In this study, we investigated the abilities of two prototype strains of HMPV (A1 [NL\1\00] and B1 [NL\1\99]) to activate RIG-I and induce type I IFNs. Despite the abilities of both HMPV-A1 and HMPV-B1 to infect and replicate in cell lines and primary cells, only the HMPV-A1 strain triggered RIG-I to induce IFNA/B gene transcription. The failure of the HMPV-B1 strain to elicit type I IFN production was dependent on the B1 phosphoprotein, which specifically prevented RIG-I-mediated sensing of HMPV viral 5' triphosphate RNA. In contrast to most cell types, plasmacytoid dendritic cells displayed a unique ability to sense both HMPV-A1 and HMPV-B1 and in this case sensing was via TLR7 rather than RIG-I. Collectively, these data reveal differential mechanisms of sensing for two closely related viruses, which operate in cell type-specific manners.
Asunto(s)
ARN Helicasas DEAD-box/metabolismo , Metapneumovirus/inmunología , Fosfoproteínas/metabolismo , Receptor Toll-Like 7/metabolismo , Interferencia Viral/inmunología , Animales , Línea Celular , Línea Celular Tumoral , Chlorocebus aethiops , Proteína 58 DEAD Box , ARN Helicasas DEAD-box/antagonistas & inhibidores , ARN Helicasas DEAD-box/fisiología , Regulación Viral de la Expresión Génica/inmunología , Humanos , Inmunidad Innata , Interferón-alfa/biosíntesis , Interferón-alfa/genética , Interferón beta/biosíntesis , Interferón beta/genética , Ligandos , Metapneumovirus/genética , Metapneumovirus/patogenicidad , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infecciones por Paramyxoviridae/inmunología , Infecciones por Paramyxoviridae/metabolismo , Infecciones por Paramyxoviridae/virología , Fosfoproteínas/genética , ARN Viral/genética , Receptores Inmunológicos , Especificidad de la Especie , Receptor Toll-Like 7/deficiencia , Receptor Toll-Like 7/fisiología , Células VeroRESUMEN
The accumulation of cross-immunity in the host population is an important factor driving the antigenic evolution of viruses such as influenza A. Mathematical models have shown that the strength of temporary non-specific cross-immunity and the basic reproductive number are both key determinants for evolutionary branching of the antigenic phenotype. Here we develop deterministic and stochastic versions of one such model. We examine how the time of emergence or introduction of a novel strain affects co-existence with existing strains and hence the initial establishment of a new evolutionary branch. We also clarify the roles of cross-immunity and the basic reproductive number in this process. We show that the basic reproductive number is important because it affects the frequency of infection, which influences the long term immune profile of the host population. The time at which a new strain appears relative to the epidemic peak of an existing strain is important because it determines the environment the emergent mutant experiences in terms of the short term immune profile of the host population. Strains are more likely to coexist, and hence to establish a new clade in the viral phylogeny, when there is a significant time overlap between their epidemics. It follows that the majority of antigenic drift in influenza is expected to occur in the earlier part of each transmission season and this is likely to be a key surveillance period for detecting emerging antigenic novelty.
Asunto(s)
Antígenos Virales/inmunología , Gripe Humana/inmunología , Viabilidad Microbiana/inmunología , Orthomyxoviridae/inmunología , Variación Antigénica/inmunología , Variación Antigénica/fisiología , Reacciones Cruzadas/fisiología , Evolución Molecular , Interacciones Huésped-Patógeno/inmunología , Humanos , Gripe Humana/virología , Modelos Biológicos , Orthomyxoviridae/genética , Orthomyxoviridae/fisiología , Filogenia , Interferencia Viral/inmunologíaRESUMEN
BACKGROUND/AIMS: Both hepatitis B virus (HBV) and hepatitis C virus (HCV) replicate in the liver and show resistance against innate immunity and interferon (IFN) treatment. Whether there is interference between these two viruses is still controversial. We investigated the interference between these two viruses and the mode of resistance against IFN. METHODS: We performed infection experiments with either or both of the two hepatitis viruses in human hepatocyte chimeric mice. Huh7 cell lines with stable production of HBV were also established and transfected with HCV JFH1 clone. Mice and cell lines were treated with IFN. The viral levels in mice sera and culture supernatants and messenger RNA levels of IFN-stimulated genes were measured. RESULTS: No apparent interference between the two viruses was seen in vivo. Only a small (0.3 log) reduction in serum HBV and a rapid reduction in HCV were observed after IFN treatment, regardless of infection with the other virus. In in vitro studies, no interference between the two viruses was observed. The effect of IFN on each virus was not affected by the presence of the other virus. IFN-induced reductions of viruses in culture supernatants were similar to those in in vivo study. CONCLUSIONS: No interference between the two hepatitis viruses exists in the liver in the absence of hepatitis. The mechanisms of IFN resistance of the two viruses target different areas of the IFN system.
Asunto(s)
Hepacivirus/inmunología , Virus de la Hepatitis B/inmunología , Hepatocitos/inmunología , Hepatocitos/virología , Interferón Tipo I/farmacología , Interferencia Viral/inmunología , Animales , Línea Celular , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepacivirus/fisiología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/fisiología , Hepatocitos/efectos de los fármacos , Hepatocitos/trasplante , Humanos , Inmunidad Innata , Técnicas In Vitro , Ratones , Ratones SCID , Proteínas Recombinantes , Transfección , Quimera por Trasplante , Trasplante Heterólogo , Carga Viral/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Replicación Viral/inmunologíaRESUMEN
Both human CMV and murine CMV (MCMV) elicit large CD8 T cell responses, despite the potent effects of viral genes that interfere with the MHC class I (MHC I) pathway of Ag presentation. To investigate the impact of immune evasion on CD8 T cell priming, we infected mice with wild-type (wt) MCMV or a mutant lacking its MHC I immune evasion genes, Deltam4+m6+m152 MCMV. In acute infection, the two viruses elicited a CD8 T cell response to 26 peptide epitopes that was virtually identical in total size, kinetics, and immunodominance hierarchy. This occurred despite results demonstrating that primary DCs are susceptible to the effects of MCMV's MHC I immune evasion genes. Eight months later, responses to both wt and mutant MCMV displayed the same CD8 T cell "memory inflation" and altered immunodominance that characterize the transition to chronic MCMV infection in C57BL/6 mice. Taken together, these findings suggest either that cross-priming dominates over direct CD8 T cell priming in both acute and chronic MCMV infection, or else that the MHC I immune evasion genes of MCMV are unable to alter direct CD8 T cell priming in vivo. At 2 years postinfection, differences in CD8 T cell immunodominance emerged between individual mice, but on average there were only slight differences between wt and mutant virus infections. Overall, the data indicate that the presence or absence of MHC I immune evasion genes has remarkably little impact on the size or specificity of the MCMV-specific CD8 T cell response over an entire lifetime of infection.
Asunto(s)
Presentación de Antígeno/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Epítopos Inmunodominantes/metabolismo , Muromegalovirus/inmunología , Interferencia Viral/inmunología , Enfermedad Aguda , Animales , Antígenos Ly/biosíntesis , Antígenos Ly/metabolismo , Linfocitos T CD8-positivos/virología , Línea Celular , Línea Celular Tumoral , Células Cultivadas , Enfermedad Crónica , Citotoxicidad Inmunológica , Inmunidad Innata , Epítopos Inmunodominantes/biosíntesis , Lectinas Tipo C/biosíntesis , Lectinas Tipo C/metabolismo , Melanoma Experimental , Ratones , Ratones Endogámicos C57BL , Receptores Similares a Lectina de Células NKRESUMEN
In 2003, the Nebraska Public Health Laboratory tested more than 10,371 serum and 516 cerebral spinal fluid specimens. Results showed that without performing the interfering factors screen for specimens in the low positive index value range of >1.1 to Asunto(s)
Anticuerpos Antivirales/sangre
, Inmunoglobulina M
, Interferencia Viral/inmunología
, Fiebre del Nilo Occidental/diagnóstico
, Virus del Nilo Occidental/inmunología
, Nebraska
, Estudios Prospectivos
, Juego de Reactivos para Diagnóstico
, Estudios Retrospectivos
, Pruebas Serológicas
, Fiebre del Nilo Occidental/sangre
, Fiebre del Nilo Occidental/inmunología
RESUMEN
Human T cell leukemia virus (HTLV) type-2 is a human retrovirus whose infection has not been tightly linked to human diseases. However, the fairly high prevalence of this infection among HIV-1-positive individuals indicates the importance of better understanding the potential interference of HTLV-2 infection on HIV-1 infection and AIDS. We previously demonstrated that one signature of PBMC freshly derived from HIV-1-infected individuals is the constitutive activation of a C-terminal truncated STAT5 (STAT5Delta). Therefore, we analyzed the potential activation of STATs in HTLV-2 monoinfected and HTLV-2/HIV-1 dually infected individuals. We observed that PBMC of HTLV-2-infected individuals do not show STAT activation unless they are cultivated ex vivo, in the absence of any mitogenic stimuli, for at least 8 h. The emergence of STAT activation, namely of STAT1, in culture was mostly related to the secretion of IFN-gamma. Of note, this phenomenon is not only a characteristic feature of HTLV-2-infected individuals but also occurred with PBMC of HIV-1(+) individuals. Surprisingly, HTLV-2/HIV-1 coinfection resulted in low/absent STAT activation in vivo that paralleled a diminished secretion of IFN-gamma after ex vivo cultivation. Our findings indicate that both HTLV-2 and HIV-1 infection prime T lymphocytes for STAT1 activation, but they also highlight an interference exerted by HTLV-2 on HIV-1-induced STAT1 activation. Although the nature of such a phenomenon is unclear at the present, these findings support the hypothesis that HTLV-2 may interfere with HIV-1 infection at multiple levels.
Asunto(s)
Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/inmunología , Infecciones por HTLV-II/inmunología , Infecciones por HTLV-II/virología , Virus Linfotrópico T Tipo 2 Humano/inmunología , Proteínas de la Leche , Transducción de Señal/inmunología , Interferencia Viral/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/virología , Células Cultivadas , Proteínas de Unión al ADN/metabolismo , Infecciones por VIH/complicaciones , Infecciones por HTLV-II/complicaciones , Humanos , Interferón gamma/biosíntesis , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/virología , Factor de Transcripción STAT1 , Factor de Transcripción STAT5 , Transactivadores/metabolismoRESUMEN
BACKGROUND: Acute hepatitis A virus (HAV) infection can cause severe hepatitis especially in patients with underlying chronic liver disease. In patients with pre-existing chronic hepatitis B (HBV) acute HAV infection can suppress HBV replication. The exact mechanism of HBV suppression during acute HAV infection is still a subject of debate. One mechanism may be the production of HAV infection-induced cytokines leading to suppression of HBV replication and viral clearance. AIM: To evaluate cytokine production and HBV-specific lympho-proliferative responses (LPR) during acute HAV infection in a patient with chronic HBV infection-clearing markers of active HBV replication. DESIGN: Early detection of a case of acute HAV infection in an HBeAg-positive, HBV DNA-positive chronic HBV patient treated with lamivudine. RESULTS: At the time of HAV infection a sharp peak in the gamma-interferon (IFN-gamma) level occurred just before the rise in serum transaminase activity. This was subsequently followed by a decrease in HBV DNA and HBeAg below the limit of detection of the assay. However the HBV-specific T-cell response was not modified. After resolution of the acute HAV infection and withdrawal of antiviral therapy HBV replication relapsed. CONCLUSION: The sharp rise in IFN-gamma production mediated by the acute HAV infection may be pivotal in the suppression of HBV replication in chronic hepatitis B.