Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais/imunologia , Humanos , Imunidade Humoral , ReinfecçãoRESUMO
A 40-year-old female was found to have strongly neutralizing SARS-CoV-2 breastmilk IgA and IgG antibodies reactive against multiple SARS-CoV-2 antigens at 2.5 months after documented infection with SARS-CoV-2. At 6.5 months following the infection, she remained positive for breastmilk and serum SARS-CoV-2 neutralizing antibodies. Holder breast milk pasteurization did not diminish SARS-CoV-2 antibody titres but it reduced its neutralizing capacity, while serum heat inactivation had no negative effect on SARS-CoV-2 serum antibody levels and neutralizing capacity. Current data on SARS-CoV-2 and breastmilk are reviewed.
Assuntos
Anticorpos Antivirais/análise , Antígenos Virais/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Leite Humano/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Feminino , Humanos , Ligação Proteica , Domínios ProteicosRESUMO
Immune responses against multiple epitopes are required for the prevention of hepatitis C virus (HCV) infection, and the progression to phase I trials of candidates may be guided by comparative immunogenicity studies in non-human primates. Four vectors, DNA, SFV, human serotype 5 adenovirus (HuAd5) and Modified Vaccinia Ankara (MVA) poxvirus, all expressing hepatitis C virus Core, E1, E2 and NS3, were combined in three prime-boost regimen, and their ability to elicit immune responses against HCV antigens in rhesus macaques was explored and compared. All combinations induced specific T-cell immune responses, including high IFN-γ production. The group immunized with the SFV+MVA regimen elicited higher E2-specific responses as compared with the two other modalities, while animals receiving HuAd5 injections elicited lower IL-4 responses as compared with those receiving MVA. The IFN-γ responses to NS3 were remarkably similar between groups. Only the adenovirus induced envelope-specific antibody responses, but these failed to show neutralizing activity. Therefore, the two novel regimens failed to induce superior responses as compared with already existing HCV vaccine candidates. Differences were found in response to envelope proteins, but the relevance of these remain uncertain given the surprisingly poor correlation with immunogenicity data in chimpanzees, underlining the difficulty to predict efficacy from immunology studies.
Assuntos
Linfócitos B/imunologia , Epitopos/genética , Hepacivirus/imunologia , Linfócitos T/imunologia , Vacinas contra Hepatite Viral/imunologia , Adenoviridae/genética , Animais , Linhagem Celular , Cricetinae , Epitopos/imunologia , Vetores Genéticos/genética , Imunogenicidade da Vacina , Interferon gama/sangue , Interleucina-4/sangue , Macaca mulatta , Masculino , Vaccinia virus/genética , Vacinas contra Hepatite Viral/genéticaRESUMO
Canine hepacivirus (CHV) has recently been identified in liver and respiratory tract samples from dogs, and comparative phylogenetic analysis has confirmed it to be the closest genetic relative of hepatitis C virus (HCV) described to date. CHV offers great potential as a model system for HCV, but only if the underlying processes of infection and pathogenesis are similar for both viruses. However, it is not yet clear if CHV is hepatotrophic. Canine chronic hepatitis (CH) is a common and usually idiopathic disease that shares similar histological features to that of HCV infection of humans. To date, no study has attempted to determine whether CHV is involved in the aetiology of liver disease in dogs. We employed two nested PCR assays, using primers targeting regions of the helicase domain of CHV NS3, to identify viral nucleic acids in liver samples from 100 dogs with CH of unknown cause in the UK. We also used a sensitive luciferase immunoprecipitation system (LIPS) assay to screen serum samples from these dogs for the presence of anti-CHV antibodies. Surprisingly, there was no evidence of exposure to, or a carrier state of, CHV in this large cohort, suggesting that the virus is not associated with CH in UK dogs. Future work, including transmission studies, is required to understand the pathogenesis of CHV in canids before it can be proposed as a surrogate model for HCV-induced liver disease in man.
Assuntos
Doenças do Cão/etiologia , Hepacivirus/genética , Hepatite C Crônica/veterinária , Hepatopatias/veterinária , Animais , Doenças do Cão/diagnóstico , Cães , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/sangue , Anticorpos Anti-Hepatite C/imunologia , RNA Viral/genética , Proteínas não Estruturais Virais/imunologiaRESUMO
BACKGROUND AND METHODS: To investigate the seroprevalence of polyomavirus infections in macaques, we analyzed 1579 sera from nine different species for antibodies cross-reactive with simian virus 40 (SV40) in an enzyme-linked immunosorbent assay. Most samples were collected from captive animals, but we also investigated a colony of free-ranging Barbary macaques (Macaca sylvanus). RESULTS: High seropositive rates were found in rhesus macaques (Macaca mulatta; 74.7%), cynomolgus macaques (Macaca fascicularis; 44.8%) and Tonkean macaques (Macaca tonkeana; 41.7%), especially in animals imported from China. Low rates were measured in cynomolgus macaques from Mauritius (8.8%), and in Barbary macaques (1.4%). Seropositivity was age-dependent increasing to >70% in animals of 5 years and older. CONCLUSIONS: High seroprevalence rates were found in different species of macaques, dependent on their origin. Very low infection rates found in Barbary macaques and cynomolgus macaques from Mauritius suggest that these animals in the wild are not commonly infected by SV40-like viruses.
Assuntos
Animais Selvagens , Animais de Zoológico , Anticorpos Antivirais/sangue , Macaca/virologia , Infecções por Polyomavirus/veterinária , Animais , Proteínas do Capsídeo/imunologia , Maurício/epidemiologia , Infecções por Polyomavirus/epidemiologia , Estudos SoroepidemiológicosRESUMO
The rapidly spreading HIV epidemic requires a vaccine that elicits potent mucosal immunity to halt or slow transmission. Induction of these responses will depend on the use of appropriate adjuvants and targeting of the mucosal immune system. Previously, immune stimulating complexes (ISCOM) have shown great potency as adjuvant in the induction of mucosal responses in mice and systemic responses in non-human primates. In this study, HIV formulated in PR8-Flu ISCOM adjuvant was applied to immunize rhesus macaques against HIV; targeting the mucosa either via intranasal (IN) application or via targeted lymph node immunization (TLNI). While, strong systemic, HIV specific, cytokine, lymphoproliferative, and antibody responses were induced via the TLNI route, the IN application generated only low responses. Furthermore, all four animals immunized via TLNI developed vaginal IgA antibodies against gp120. In conclusion, in contrast to what has been demonstrated in mice, the IN application of PR8-Flu ISCOM did not induce strong immune responses in rhesus macaques unlike those immunized by the TLNI route.
Assuntos
Vacinas contra a AIDS/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Anticorpos Anti-HIV/análise , Infecções por HIV/imunologia , HIV-1/imunologia , ISCOMs/administração & dosagem , Imunização , Vacinas contra a AIDS/imunologia , Administração Intranasal , Animais , Especificidade de Anticorpos , Feminino , Proteína do Núcleo p24 do HIV/administração & dosagem , Proteína do Núcleo p24 do HIV/imunologia , Proteína gp120 do Envelope de HIV/administração & dosagem , Proteína gp120 do Envelope de HIV/imunologia , Humanos , Esquemas de Imunização , Imunoglobulina A/análise , Injeções Intralinfáticas , Macaca mulatta , Vacinas de Subunidades Antigênicas/administração & dosagem , Vagina/imunologiaRESUMO
Public awareness of the human health risks of zoonotic infections has grown in recent years. Currently, concern of H5N1 flu transmission from migratory bird populations has increased with foci of fatal human cases. This comes on the heels of other major zoonotic viral epidemics in the last decade. These include other acute emerging or re-emerging viral diseases such as severe acute respiratory syndrome (SARS), West-Nile virus, Ebola virus, monkeypox, as well as the more inapparent insidious slow viral and prion diseases. Virus infections with zoonotic potential can become serious killers once they are able to establish the necessary adaptations for efficient human-to-human transmission under circumstances sufficient to reach epidemic proportions. The monitoring and early diagnosis of these potential risks are overlapping frontiers of human and veterinary medicine. Here, current viral zoonotics and evolving threats are reviewed.
Assuntos
Doenças Transmissíveis Emergentes , Infecções por Vírus de RNA , Zoonoses , Animais , Aves , Doenças Transmissíveis Emergentes/diagnóstico , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/transmissão , Surtos de Doenças , Diagnóstico Precoce , Humanos , Virus da Influenza A Subtipo H5N1/patogenicidade , Influenza Aviária/transmissão , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Influenza Humana/transmissão , Infecções por Vírus de RNA/diagnóstico , Infecções por Vírus de RNA/epidemiologia , Infecções por Vírus de RNA/transmissão , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/patogenicidade , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/transmissão , Zoonoses/epidemiologia , Zoonoses/transmissãoRESUMO
Noroviruses, with Norwalk virus as the prototype strain, are the most common cause of viral gastroenteritis in people of all ages. Limited information on the immunology of Norovirus infections has been obtained by studies both in the natural setting and in experimentally infected volunteers. Interpretation of these studies is difficult due to the lack of information on the history of Norovirus exposure and the cross-reactivity of antibodies. An animal model for Norovirus infections would be important to study the immune response, e.g., for vaccine assessment. In the present study the susceptibility of common marmosets, cotton top tamarins, cynomolgus, and rhesus macaques to Norovirus infection was tested. Following oral inoculation, low level replication may have occurred in common marmosets and cotton top tamarins but not in cynomolgus macaques, based on short-term viral shedding; neither clinical symptoms nor antibody responses were observed in these species. In contrast, rhesus macaques were found susceptible to Norwalk virus infection as one animal shed virus for a longer period of time and developed Norwalk virus specific IgM and IgG responses. Further research on Norovirus susceptibility in rhesus macaques may yield an animal model to study the immune response and pathogenesis after Norovirus infection.
Assuntos
Infecções por Caliciviridae/imunologia , Norovirus/isolamento & purificação , Norovirus/patogenicidade , Sistema ABO de Grupos Sanguíneos , Animais , Anticorpos Antivirais/sangue , Doenças dos Símios Antropoides/epidemiologia , Antígenos de Grupos Sanguíneos , Infecções por Caliciviridae/sangue , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/veterinária , Callithrix/imunologia , Callithrix/virologia , Modelos Animais de Doenças , Fezes/virologia , Macaca fascicularis/imunologia , Macaca fascicularis/virologia , Macaca mulatta/imunologia , Macaca mulatta/virologia , Doenças dos Macacos/epidemiologia , Norovirus/imunologia , Pan troglodytes/virologia , RNA Viral/isolamento & purificação , Saguinus/imunologia , Saguinus/virologia , Eliminação de Partículas Virais/genéticaRESUMO
Cell-surface CCR5 is a major coreceptor with CD4 glycoprotein, mediating cellular entry of CCR5 strains of HIV-1 or SIV. We targeted the SIV CCR5 coreceptor in a combined CCR5-SIV antigen immunization strategy. Rhesus macaques were immunized i.m. with the 70 kDa heat shock protein (HSP70) covalently linked to the CCR5 peptides, SIV gpl20 and p27. Intravenous challenge with SIV mac 8980 prevented SIV infection or decreased the viral load with the CCR5-SIV combined vaccine. CC chemokines and antibodies which block and downmodulateCCR5 were induced, as well as immune responses to the subunit SIV antigens. This novel vaccination strategy complements cognate immunity to SIV with innate immunity to the CCR5 coreceptor of SIV.
Assuntos
Receptores CCR5/imunologia , Vacinas contra a SAIDS/uso terapêutico , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Sequência de Aminoácidos , Animais , Anticorpos Antivirais/análise , Anticorpos Antivirais/biossíntese , Antígenos de Superfície/imunologia , Antígenos Virais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Produtos do Gene rex/genética , Produtos do Gene rex/imunologia , Proteínas de Choque Térmico HSP70/metabolismo , Esquemas de Imunização , Imunoglobulina A/análise , Imunoglobulina A/biossíntese , Imunoglobulina G/análise , Imunoglobulina G/biossíntese , Cinética , Macaca mulatta , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Dados de Sequência Molecular , Mycobacterium tuberculosis/imunologia , Linfócitos T/imunologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologiaRESUMO
The immunogenicity and protective efficacy of a DNA and recombinant modified vaccinia Ankara (MVA) vaccine administered by two different routes were investigated. DNA expressing HIV-1 IIIB env, gag, RT, rev, tat and nef, and MVA expressing HIV-1 IIIB nef, tat and rev and simian immunodeficiency virus (SIV) macJ5 gag/pol and vaccinia HIV-1 env, were used as immunogens. Four cynomolgus macaques received DNA intramuscularly (i.m.) at month 0 and intrarectally (i.r.) and intra-orally (i.o.) at 2 months, followed by MVA i.m. at 4 months and i.r. and i.o. at 8 months. Another group of four monkeys received the same immunogens but only i.m. Overall, stronger cellular immune responses measured by ELISPOT and T-cell proliferation assay were detected in the group primed i.m. and boosted mucosally. Following homologous intravenous simian-human immunodeficiency virus (SHIV) challenge, one of eight vaccinated animals was completely protected. This monkey, immunized i.m. and i.r.+i.o., exhibited the highest levels of HIV Env, Nef and Tat antibodies, high HIV Tat cytotoxic T-lymphocyte activity and T-lymphocyte proliferative responses to HIV Env. Four weeks post-challenge none of the monkeys immunized i.m. and i.r.+i.o., and only two out of four animals immunized i.m., demonstrated detectable plasma viral RNA levels. In contrast, all eight control animals had demonstrable plasma viral RNA levels 4 weeks post-challenge. Thus, stronger cellular immune responses and reduction of challenge virus burden were demonstrated in animals immunized i.m. as well as mucosally, compared with animals immunized i.m. only. The breadth and magnitude of the induced immune responses correlated with protective efficacy.
Assuntos
Vacinas contra a SAIDS/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vacinas de DNA/imunologia , Vaccinia virus/imunologia , Animais , Anticorpos Anti-HIV/sangue , Imunização , Interferon gama/biossíntese , Macaca fascicularis , Vacinas contra a SAIDS/administração & dosagem , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Linfócitos T Citotóxicos/imunologia , Vacinas de DNA/administração & dosagem , Carga ViralRESUMO
Prophylactic hepatitis C virus (HCV) vaccine trials with human volunteers are pending. There is an important need for immunological end points which correlate with vaccine efficacy and which do not involve invasive procedures, such as liver biopsies. By using a multicomponent DNA priming-protein boosting vaccine strategy, naïve chimpanzees were immunized against HCV structural proteins (core, E1, and E2) as well as a nonstructural (NS3) protein. Following immunization, exposure to the heterologous HCV 1b J4 subtype resulted in a peak of plasma viremia which was lower in both immunized animals. Compared to the naïve infection control and nine additional historical controls which became chronic, vaccinee 2 (Vac2) rapidly resolved the infection, while the other (Vac1) clearly controlled HCV infection. Immunization induced antibodies, peptide-specific gamma interferon (IFN-gamma), protein-specific lymphoproliferative responses, IFN-gamma, interleukin-2 (IL-2), and IL-4 T-helper responses in both vaccinees. However, the specificities were markedly different: Vac2 developed responses which were lower in magnitude than those of Vac1 but which were biased towards Th1-type cytokine responses for E1 and NS3. This proof-of-principle study in chimpanzees revealed that immunization with a combination of nonstructural and structural antigens elicited T-cell responses associated with an alteration of the course of infection. Our findings provide data to support the concept that the quality of the response to conserved epitopes and the specific nature of the peripheral T-helper immune response are likely pivotal factors influencing the control and clearance of HCV infection.
Assuntos
Hepacivirus/imunologia , Hepatite C Crônica/prevenção & controle , Células Th1/imunologia , Células Th2/imunologia , Vacinas contra Hepatite Viral/imunologia , Animais , Citocinas/biossíntese , Hepacivirus/patogenicidade , Anticorpos Anti-Hepatite C/sangue , Antígenos da Hepatite C/imunologia , Hepatite C Crônica/imunologia , Humanos , Imunização , Ativação Linfocitária/imunologia , Pan troglodytes , Proteínas do Core Viral/imunologia , Vacinas contra Hepatite Viral/administração & dosagem , Proteínas não Estruturais Virais/imunologiaRESUMO
Before autoimmune diseases in humans can be treated with gene therapy, the safety and efficacy of the used vectors must be tested in valid experimental models. Monkeys, such as the rhesus macaque or the common marmoset, provide such models. This publication reviews the state of the art in monkey models for rheumatoid arthritis and multiple sclerosis and the (few) gene therapy experiments that have been performed in these models.
Assuntos
Doenças Autoimunes/terapia , Terapia Genética/métodos , Modelos Animais , Primatas , Animais , Artrite/imunologia , Artrite/terapia , Doenças Autoimunes/imunologia , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/terapia , Vetores Genéticos/administração & dosagem , Haplorrinos , Humanos , Interleucina-4/genética , Interleucina-4/imunologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/terapiaRESUMO
A retrospective study spanning 20 years was undertaken to investigate the prevalence and modes of transmission of a simian T-cell lymphotropic virus (STLV) in a closed breeding colony of chimpanzees. Of the 197 animals tested, 22 had antibodies that were cross-reactive with human T-cell lymphotropic virus type-1 (HTLV-I) antigens. The specificity of the antibody response was confirmed by Western blot analysis and the presence of a persistent virus infection was established by PCR analysis of DNA from peripheral blood mononuclear cells. Sequence analysis revealed that the virus infecting these chimpanzees was not HTLV-I but STLV(cpz), a virus that naturally infects chimpanzees. The limited number of transmission events suggested that management practices of social housing of family units away from troops of mature males might have prevented the majority of cases of transmission. Evidence for transmission by blood-to-blood contact was documented clearly in at least one instance. In contrast, transmission from infected mother to child was not observed, suggesting that this is not a common route of transmission for STLV in this species, which is in contrast to HTLV-1 in humans.
Assuntos
Doenças dos Símios Antropoides/transmissão , Infecções por Deltaretrovirus/veterinária , Pan troglodytes , Vírus Linfotrópico T Tipo 1 de Símios/genética , Animais , Anticorpos Antivirais/sangue , Doenças dos Símios Antropoides/sangue , Doenças dos Símios Antropoides/virologia , Infecções por Deltaretrovirus/transmissão , Transmissão de Doença Infecciosa , Feminino , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Leucócitos Mononucleares/virologia , Masculino , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase , Prevalência , Estudos Retrospectivos , Fatores Sexuais , Vírus Linfotrópico T Tipo 1 de Símios/química , Vírus Linfotrópico T Tipo 1 de Símios/classificação , Proteínas do Envelope Viral/genéticaRESUMO
OBJECTIVE: HIV-1 infection in humans has been reported to lead to a shift in the cytokine balance, with a relative decrease in T helper 1 type cytokines, especially IL-2. On the basis of the expression of CD45RA, in combination with homing markers CD62L or alpha4beta7, T helper cells can be sub-divided into naive, activated naive, central memory and effector memory cells as well as gut-homing subpopulations. In addition, each subset may have the potential to express distinct cytokines. At present it is unclear whether the changes in cytokine expression observed in HIV-1-infected individuals are secondary to changes within the composition of CD4 T cell subsets or are caused by changes in cytokine expression within each subset. MATERIALS AND METHODS: A new technique was developed to detect cytokine expression in phorbol 12-myristate 13-acetate/ionomycin-activated CD62L and alpha4beta7-expressing CD4 T cell subsets, using the protease inhibitor KD-IX-73-4. RESULTS: In SIV-infected macaques that develop AIDS a marked decrease in IL-2 expression was found within central, effector, or gut-homing memory cell subsets, whereas the expression of IL-2 in naive T cell subsets remained unaffected. This reduced IL-2 expression by memory cells and not a loss of the frequency of CD4 memory cells accounted for the reduced expression of IL-2 by CD4 T cells during SIV infection. CONCLUSION: As defined by the cell surface markers utilized, it appears that progression to AIDS is associated with functional impairment of memory cells, but not changes in lymphocyte circulation patterns.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Memória Imunológica/imunologia , Interleucina-2/metabolismo , Síndrome de Imunodeficiência Adquirida dos Símios/fisiopatologia , Vírus da Imunodeficiência Símia/imunologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Citometria de Fluxo/métodos , Humanos , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologiaRESUMO
The severity of the AIDS epidemic clearly emphasises the urgent need to expedite HIV vaccine candidates into clinical trials. Prophylactic HIV vaccine candidates have been evaluated in non-human primates. Based on specific proof of principle studies the first phase III clinical studies have recently begun in humans. However, a truly effective HIV vaccine is not yet at hand and many problems related to specific properties of the virus remain to be overcome. Previously proven empirical approaches have largely failed and now rational thinking based on an understanding of immunity to lentiviral infections is needed. This review addresses the scientific problems and complications facing the development of an HIV vaccine as well as the possible strategies currently available to overcome these problems. Recent attention has focussed on identifying the immune correlates and mechanisms of protection from either HIV infection or protection from disease progression. Based on these observations, the logic and rational behind the development of multiple component vaccine strategies are highlighted.
Assuntos
Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/administração & dosagem , Vetores Genéticos , HIV/classificação , Humanos , Imunidade nas Mucosas , Vacinas de DNA/imunologia , Vacinas Sintéticas/imunologiaRESUMO
Dendritic cells (DC) have been implicated in the pathogenesis of both human and simian immunodeficiency viruses (HIV and SIV, respectively). The DC-specific HIV-1 trans-receptor DC-SIGN is thought to be essential for viral dissemination by DC. Abundant expression in lymphoid tissues also implies a function for DC-SIGN in chronic HIV-1 infections, in facilitating persistent infection of T cells. We have therefore isolated the rhesus macaque and chimpanzee homologues of DC-SIGN to investigate their function in a primate model. Both rhesus macaque and chimpanzee DC-SIGN are highly similar to the human homologue. Three monoclonal antibodies against human DC-SIGN, AZN-D1, -D2 and -D3, cross-react with rhesus macaque DC-SIGN, whereas AZN-D2 does not cross-react with chimpanzee DC-SIGN. The primate homologues are abundantly expressed in lymphoid tissues such as lymph nodes, as well as in mucosal tissues involved in sexual transmission of HIV-1, and are functionally similar to human DC-SIGN. They have a high affinity for the immunological ligands of DC-SIGN: ICAM-2 and -3. Moreover, both homologues bind the HIV-1 envelope glycoprotein gp120 and therefore can act as a HIV-1 trans-receptor in the same way as human DC-SIGN. These data demonstrate that primate models are suitable to further dissect the role of DC-SIGN in the transmission and pathogenesis of infection with immunodeficiency viruses.
Assuntos
Moléculas de Adesão Celular , Lectinas Tipo C , Lectinas/imunologia , Macaca mulatta/imunologia , Glicoproteínas de Membrana , Pan troglodytes/imunologia , Receptores de Superfície Celular/imunologia , Receptores de HIV/imunologia , Vírus da Imunodeficiência Símia/imunologia , Proteínas do Envelope Viral , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais , Sequência de Bases , Reações Cruzadas , DNA Complementar/genética , Células Dendríticas/imunologia , Expressão Gênica , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Humanos , Lectinas/genética , Ligantes , Macaca mulatta/genética , Dados de Sequência Molecular , Pan troglodytes/genética , Receptores de Superfície Celular/genética , Receptores de HIV/genética , Homologia de Sequência de Aminoácidos , Especificidade da EspécieRESUMO
We obtained sealed vials of two different polio vaccine lots, expiration date 1955, which were used in the first U.S. polio vaccine campaign. These early lots were pulled from the market because they contained live infectious poliovirus which caused polio in some of the vaccines. Theoretically, these vaccines could have contained other infectious retroviruses, including HIV. No viral sequences were detected using RT-PCR analyses with primers capable of amplifying chimpanzee SIV and HIV-1-related viruses nor with primers for macaque SIV, sooty mangabey SIV, and HIV-2-related viruses. Poliovirus sequences were readily amplified by RT-PCR, suggesting that the technique used would have detected SIV or HIV sequences, if present.
Assuntos
Contaminação de Medicamentos , HIV/isolamento & purificação , Vacinas contra Poliovirus/química , Vírus da Imunodeficiência Símia/isolamento & purificação , Animais , Cercocebus atys , HIV-1/isolamento & purificação , HIV-2/isolamento & purificação , Humanos , Pan troglodytes , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The nef genes of human immunodeficiency virus and simian immunodeficiency virus (SIV) overlap about 80% of the U3 region of the 3' long terminal repeat (LTR) and contain several essential cis-acting elements (here referred to as the TPI region): a T-rich region, the polypurine tract, and attachment (att) sequences required for integration. We inactivated the TPI region in the nef reading frame of the pathogenic SIVmac239 clone (239wt) by 13 silent point mutations. To restore viral infectivity, intact cis-regulatory elements were inserted just downstream of the mutated nef gene. The resulting SIV genome contains U3 regions that are 384 bp shorter than the 517-bp 239wt U3 region. Overall, elimination of the duplicated Nef coding sequences truncates the proviral genome by 350 bp. Nonetheless, it contains all known coding sequences and cis-acting elements. The TPI mutant virus expressed functional Nef and replicated like 239wt in all cell culture assays and in vivo in rhesus macaques. Notably, these SIVmac constructs allow us to study Nef function in the context of replication-competent viruses without the restrictions of overlapping LTR sequences and important cis-acting elements. The genomes of all known primate lentiviruses contain a large overlap between nef and the U3 region. We demonstrate that this conserved genomic organization is not obligatory for efficient viral replication and pathogenicity.
Assuntos
Genes nef , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/fisiologia , Vírus da Imunodeficiência Símia/patogenicidade , Sequências Repetidas Terminais/genética , Replicação Viral , Animais , Linhagem Celular , Produtos do Gene nef/metabolismo , Macaca mulatta , Mutação , Reação em Cadeia da Polimerase , Vírus da Imunodeficiência Símia/genética , TransfecçãoRESUMO
Recent evidence suggests a much higher prevalence of human immunodeficiency virus type 1 (HIV-1) recombinants than previously anticipated. These recombinants arise from secondary HIV infections in individuals already infected with the virus. It remains unclear why some individuals acquire secondary HIV-1 infections and others do not. To address this question, a study was undertaken of a small cohort of chimpanzees with well-defined HIV-1 infection. After exposure to an infectious dose of heterologous primary isolate, 4 of 8 HIV-1 seropositive chimpanzees resisted secondary infection, whereas 2 naive controls became readily infected. Only animals who were immunologically boosted were protected. Protection from heterologous secondary exposure appeared to be related to the repertoire of the cytolytic CD8(+) T cell responses to HIV-1. Data suggested that immunologic boosting by HIV-1 antigens or exposure to subinfectious doses of virus may be important events in sustaining sufficient immunity to prevent secondary infections from occurring.
Assuntos
Vacinas contra a AIDS/administração & dosagem , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Linfócitos T Citotóxicos/imunologia , Vacinas contra a AIDS/imunologia , Animais , Infecções por HIV/imunologia , Pan troglodytesRESUMO
Corticosteroids are used therapeutically as potent immunosuppressive and antiinflammatory drugs for a broad spectrum of diseases. Although corticosteroids are known to inhibit the production of many cytokines in activated T cells, there is also evidence for increases in IL-4 and in some cases IFNgamma production. These conflicting results may be caused by contrary effects of corticosteroids on different cell types involved in immune regulation, for instance antigen presenting cells (APC) versus T cells. In the present study we simultaneously investigated the effect of local as well as systemic application of glucocorticoids (GCC) on the phenotype of APC in the skin as well as the lymph nodes in a model primate species, the rhesus macaque. Using a range of APC markers, including CD68, HAM56, HLA-DR, CD1a, p55, RFD-1, and costimulatory molecules CD40, CD80, and CD86 we document the close phenotypic resemblance of rhesus and human APC. We noted that topical GCC treatment specifically lead to a marked decrease in the number of CD1a expressing cells in the draining lymph nodes. However, the number of CD1a positive cells in peripheral lymph nodes was not affected by systemic GCC treatment. Importantly, by performing double staining of CD1a with RFD-1 we observed a shift in the expression pattern of these dendritic cell markers in the lymph nodes, with an increase in the number of RFD-1 single positive cells relative to CD1a single positive and CD1a/RFD-1 double positive cells. These findings suggest that GCC treatment results in the presence of phenotypically more mature APC.