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1.
Nat Commun ; 9(1): 1371, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29636452

RESUMO

HIV-1 causes chronic inflammation and AIDS in humans, whereas related simian immunodeficiency viruses (SIVs) replicate efficiently in their natural hosts without causing disease. It is currently unknown to what extent virus-specific properties are responsible for these different clinical outcomes. Here, we incorporate two putative HIV-1 virulence determinants, i.e., a Vpu protein that antagonizes tetherin and blocks NF-κB activation and a Nef protein that fails to suppress T cell activation via downmodulation of CD3, into a non-pathogenic SIVagm strain and test their impact on viral replication and pathogenicity in African green monkeys. Despite sustained high-level viremia over more than 4 years, moderately increased immune activation and transcriptional signatures of inflammation, the HIV-1-like SIVagm does not cause immunodeficiency or any other disease. These data indicate that species-specific host factors rather than intrinsic viral virulence factors determine the pathogenicity of primate lentiviruses.


Assuntos
HIV-1/patogenicidade , Especificidade de Hospedeiro , Proteínas do Vírus da Imunodeficiência Humana/imunologia , Lentivirus de Primatas/crescimento & desenvolvimento , Vírus da Imunodeficiência Símia/patogenicidade , Proteínas Virais Reguladoras e Acessórias/imunologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana/imunologia , Sequência de Aminoácidos , Animais , Antígeno 2 do Estroma da Médula Óssea/genética , Antígeno 2 do Estroma da Médula Óssea/imunologia , Complexo CD3/genética , Complexo CD3/imunologia , Chlorocebus aethiops , Feminino , Regulação da Expressão Gênica , HIV-1/crescimento & desenvolvimento , Proteínas do Vírus da Imunodeficiência Humana/genética , Humanos , Lentivirus de Primatas/patogenicidade , Ativação Linfocitária , NF-kappa B/genética , NF-kappa B/imunologia , Alinhamento de Sequência , Transdução de Sinais , Vírus da Imunodeficiência Símia/crescimento & desenvolvimento , Transcrição Gênica , Carga Viral , Proteínas Virais Reguladoras e Acessórias/genética , Virulência , Replicação Viral , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética
2.
Virology ; 474: 10-8, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25463599

RESUMO

Interferon-induced transmembrane (IFITM) proteins inhibit the entry of a large number of viruses. Not surprisingly, many viruses are refractory to this inhibition. In this study, we report that different strains of HIV and SIV are inhibited by human IFITM proteins to various degrees, with SIV of African green monkeys (SIV(AGM)) being mostly restricted by human IFITM2. Interestingly, SIV(AGM) is as much inhibited by human IFITM2 as by IFITM3 of its own host African green monkeys. Our data further demonstrate that the entry of SIV(AGM) is impaired by human IFITM2 and that this inhibition is overcome by the cholesterol-binding compound amphotericin B that also overcomes IFITM inhibition of influenza A viruses. These results suggest that IFITM proteins exploit similar mechanisms to inhibit the entry of both pH-independent primate lentiviruses and the pH-dependent influenza A viruses.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Interferons/imunologia , Lentivirus de Primatas/patogenicidade , Proteínas de Membrana/imunologia , Sequência de Aminoácidos , Animais , Células COS , Chlorocebus aethiops , Células HEK293 , HIV/imunologia , HIV/patogenicidade , HIV/fisiologia , Humanos , Vírus da Influenza A/imunologia , Vírus da Influenza A/patogenicidade , Vírus da Influenza A/fisiologia , Lentivirus de Primatas/imunologia , Lentivirus de Primatas/fisiologia , Proteínas de Membrana/genética , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos , Vírus da Imunodeficiência Símia/imunologia , Vírus da Imunodeficiência Símia/patogenicidade , Vírus da Imunodeficiência Símia/fisiologia , Células Vero , Internalização do Vírus
3.
Cell Host Microbe ; 11(2): 194-204, 2012 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-22284954

RESUMO

The human SAMHD1 protein potently restricts lentiviral infection in dendritic cells and monocyte/macrophages but is antagonized by the primate lentiviral protein Vpx, which targets SAMHD1 for degradation. However, only two of eight primate lentivirus lineages encode Vpx, whereas its paralog, Vpr, is conserved across all extant primate lentiviruses. We find that not only multiple Vpx but also some Vpr proteins are able to degrade SAMHD1, and such antagonism led to dramatic positive selection of SAMHD1 in the primate subfamily Cercopithecinae. Residues that have evolved under positive selection precisely determine sensitivity to Vpx/Vpr degradation and alter binding specificity. By overlaying these functional analyses on a phylogenetic framework of Vpr and Vpx evolution, we can decipher the chronology of acquisition of SAMHD1-degrading abilities in lentiviruses. We conclude that vpr neofunctionalized to degrade SAMHD1 even prior to the birth of a separate vpx gene, thereby initiating an evolutionary arms race with SAMHD1.


Assuntos
Cercopithecinae/genética , Evolução Molecular , Interações Hospedeiro-Patógeno , Lentivirus de Primatas/genética , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Proteínas Virais Reguladoras e Acessórias/genética , Sequência de Aminoácidos , Animais , Linhagem Celular , Cercopithecinae/imunologia , Cercopithecinae/virologia , Análise por Conglomerados , Humanos , Lentivirus de Primatas/patogenicidade , Dados de Sequência Molecular , Proteínas Monoméricas de Ligação ao GTP/genética , Proteínas Monoméricas de Ligação ao GTP/imunologia , Filogenia , Proteólise , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Proteínas Virais Reguladoras e Acessórias/metabolismo
4.
Curr HIV Res ; 9(7): 514-23, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22103835

RESUMO

The multifunctional Nef protein of primate lentiviruses is commonly considered an early viral factor that down-modulates various receptors from the cell surface and modulates several signaling pathways to facilitate viral immune evasion and to render the cell conducive for viral replication. However, Nef also acts during the late stages of infection, e.g. by increasing the infectivity of progeny virions. Just recently, it has become clear that many primate lentiviruses that have been detected in about 40 different monkey and ape species also use Nef to antagonize tetherin (BST2/CD317), a cellular factor that inhibits virus release by tethering nascent viral particles to the cell surface. Exceptions are some simian immunodeficiency viruses (SIVs) infecting Cercopithecus monkeys that employ their accessory Vpu protein to counteract the restriction by tetherin. Furthermore, pandemic HIV-1 group M strains switched from Nef to Vpu and HIV-2 group A isolates from Nef to Env after zoonotic transmission from chimpanzees and sooty mangabeys, respectively, to antagonize the tetherin restriction in humans. These evolutionary switches were most likely enforced by a deletion in the cytoplasmic domain of the human tetherin orthologue that confers resistance to Nef. Here, we summarize some of our current knowledge about Nef-mediated tetherin antagonism.


Assuntos
Produtos do Gene nef/fisiologia , HIV/fisiologia , Infecções por Lentivirus/imunologia , Lentivirus de Primatas/fisiologia , Primatas/virologia , Animais , Antígenos CD/fisiologia , Evolução Biológica , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/fisiologia , HIV-1/fisiologia , HIV-2/fisiologia , Humanos , Lentivirus de Primatas/patogenicidade , Especificidade da Espécie , Proteínas Virais Reguladoras e Acessórias/fisiologia , Liberação de Vírus/fisiologia
5.
Cell Host Microbe ; 8(1): 55-67, 2010 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-20638642

RESUMO

Retroviruses have evolved effective strategies to evade the host immune response, such as high variability and latent infection. In addition, primate lentiviruses, such as HIV-1, have acquired several "accessory" genes that antagonize antiviral host restriction factors and facilitate viral immune evasion, thereby allowing continuous and efficient viral replication despite apparently strong innate and acquired immune responses. Here, I summarize some of our current knowledge on the acquisition and function of the viral vif, vpr, vpu, and nef genes, with a particular focus on the evolution and specific properties of pandemic HIV-1 strains that may contribute to their efficient spread and high virulence.


Assuntos
Infecções por HIV/imunologia , HIV-1/imunologia , Interações Hospedeiro-Patógeno , Evasão da Resposta Imune , Infecções por Lentivirus/imunologia , Lentivirus de Primatas/imunologia , Animais , Infecções por HIV/virologia , HIV-1/patogenicidade , HIV-1/fisiologia , Humanos , Infecções por Lentivirus/virologia , Lentivirus de Primatas/patogenicidade , Lentivirus de Primatas/fisiologia , Proteínas Virais/genética , Proteínas Virais/imunologia
6.
Retrovirology ; 7: 13, 2010 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-20167081

RESUMO

BACKGROUND: The anti-viral activity of the cellular restriction factor, BST-2/tetherin, was first observed as an ability to block the release of Vpu-minus HIV-1 from the surface of infected cells. However, tetherin restriction is also counteracted by primate lentiviruses that do not express a Vpu protein, where anti-tetherin functions are provided by either the Env protein (HIV-2, SIVtan) or the Nef protein (SIVsm/mac and SIVagm). Within the primate lentiviruses, Vpu is also present in the genomes of SIVcpz and certain SIVsyk viruses. We asked whether, in these viruses, anti-tetherin activity was always a property of Vpu, or if it had selectively evolved in HIV-1 to perform this function. RESULTS: We found that despite the close relatedness of HIV-1 and SIVcpz, the chimpanzee viruses use Nef instead of Vpu to counteract tetherin. Furthermore, SIVcpz Nef proteins had activity against chimpanzee but not human tetherin. This specificity mapped to a short sequence that is present in the cytoplasmic tail of primate but not human tetherins, and this also accounts for the specificity of SIVsm/mac Nef for primate but not human tetherins. In contrast, Vpu proteins from four diverse members of the SIVsyk lineage all displayed an anti-tetherin activity that was active against macaque tetherin. Interestingly, Vpu from a SIVgsn isolate was also found to have activity against human tetherin. CONCLUSIONS: Primate lentiviruses show a high degree of flexibility in their use of anti-tetherin factors, indicating a strong selective pressure to counteract tetherin restriction. The identification of an activity against human tetherin in SIVgsn Vpu suggests that the presence of Vpu in the ancestral SIVmus/mon/gsn virus believed to have contributed the 3' half of the HIV-1 genome may have played a role in the evolution of viruses that could counteract human tetherin and infect humans.


Assuntos
Antígenos CD/metabolismo , Proteínas do Vírus da Imunodeficiência Humana/fisiologia , Lentivirus de Primatas/fisiologia , Proteínas Virais Reguladoras e Acessórias/fisiologia , Liberação de Vírus , Replicação Viral , Animais , Proteínas Ligadas por GPI , Humanos , Lentivirus de Primatas/patogenicidade , Glicoproteínas de Membrana/antagonistas & inibidores , Pan troglodytes
7.
Curr Mol Med ; 7(2): 171-84, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17346169

RESUMO

Human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), and simian immunodeficiency virus (SIV) are the etiological agents of acquired immunodeficiency syndrome (AIDS) in humans and a related disease in non-human primates. These viruses infect T cells and macrophages that express the surface glycoprotein, CD4, because this glycoprotein acts as a co-receptor for incoming virus particles. Once infection has occurred, however, the presence of CD4 poses problems for the virus life cycle, including the possibility of superinfection, premature binding of CD4 to nascent virus particles, and inhibition of virus release. Accordingly, primate immunodeficiency viruses have evolved at least two distinct mechanisms, mediated by the Nef and Vpu viral proteins, to "downregulate" CD4 in the host cells. Nef and Vpu are mainly expressed early and late, respectively, in the viral life cycle, ensuring continuous removal of CD4. Nef links mature CD4 to components of clathrin-dependent trafficking pathways at the plasma membrane, and perhaps in intracellular compartments, leading to internalization and delivery of CD4 to lysosomes for degradation. Vpu, on the other hand, interacts with newly-synthesized CD4 in the endoplasmic reticulum, linking CD4 to the SCF ubiquitin ligase and facilitating the entry of CD4 into the endoplasmic-reticulum-associated degradation pathway. These two mechanisms lead to a dramatic reduction of CD4 expression in infected cells and are essential for efficient virus replication and disease progression.


Assuntos
Antígenos CD4/metabolismo , Produtos do Gene nef/fisiologia , Lentivirus de Primatas/patogenicidade , Proteínas Virais Reguladoras e Acessórias/fisiologia , Proteínas Adaptadoras de Transporte Vesicular/química , Proteínas Adaptadoras de Transporte Vesicular/fisiologia , Animais , Regulação para Baixo , Produtos do Gene nef/química , Proteínas do Vírus da Imunodeficiência Humana , Humanos , Lentivirus de Primatas/fisiologia , Modelos Biológicos , Modelos Moleculares , Complexos Multiproteicos , Primatas , Ligação Proteica , Proteínas Virais Reguladoras e Acessórias/química , Proteínas Contendo Repetições de beta-Transducina/química , Proteínas Contendo Repetições de beta-Transducina/fisiologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana
8.
Curr HIV Res ; 4(3): 293-305, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16842082

RESUMO

Lentiviral diseases of animals have been recognized for over a century, long before HIV was recognized as the cause of AIDS. All lentiviruses cause neurological disease and productive virus replication in the CNS occurs exclusively in cells of macrophage lineage. The ability to molecularly engineer the inoculum virus, to sample the brain at many different time points from acute through terminal infection and to correlate in vivo with in vitro findings are significant advantages of animal models of HIV CNS disease. The lentiviruses can be divided into two pathogenetic groups--those that cause immunosuppression, including the lentiviruses of humans (HIV), non-human primates (SIV), cats (FIV), and cattle (BIV), and those that cause immunoproliferation, including the lentiviruses of horses (EIAV), sheep (OvLV) and goats (CAEV). Despite extensive study, no rodent lentivirus has been identified, prompting development of alternate strategies to study lentiviral pathogenesis using rodents. The immunosuppressive lentiviruses most closely recapitulate the disease manifestations of HIV infection, and both SIV and FIV have contributed significantly to our understanding of how HIV causes both central and peripheral nervous system disease.


Assuntos
Complexo AIDS Demência/etiologia , Modelos Animais de Doenças , Complexo AIDS Demência/patologia , Animais , Encéfalo/patologia , Vírus da Imunodeficiência Felina/patogenicidade , Lentivirus de Primatas/patogenicidade , Macaca , Camundongos
9.
J Med Primatol ; 34(5-6): 271-81, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16128922

RESUMO

Although live-attenuated human immunodeficiency virus-1 (HIV) vaccines may never be used clinically, these vaccines have provided the most durable protection from intravenous (IV) challenge in the simian immunodeficiency virus (SIV)/rhesus macaque model. Systemic infection with virulence attenuated-simian-human immunodeficiency virus (SHIV) 89.6 provides protection against vaginal SIV challenge. This paper reviews the findings related to the innate and adaptive immune responses and the role of inflammation associated with protection in the SHIV 89.6/SIVmac239 model. By an as yet undefined mechanism, most monkeys vaccinated with live-attenuated SHIV 89.6 mounted effective anti-viral CD8+ T cell responses while avoiding the self-destructive inflammatory cycle found in the lymphoid tissues of unprotected and unvaccinated monkeys.


Assuntos
Lentivirus de Primatas/imunologia , Lentivirus de Primatas/patogenicidade , Macaca mulatta , Doenças dos Macacos/virologia , Vacinas contra a SAIDS/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Animais , Linfócitos T CD8-Positivos/imunologia , Feminino , Doenças dos Macacos/imunologia , Doenças dos Macacos/prevenção & controle , Vacinas Atenuadas/imunologia , Vagina/virologia , Virulência
11.
J Virol ; 79(9): 5721-31, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15827187

RESUMO

Escape from specific T-cell responses contributes to the progression of human immunodeficiency virus type 1 (HIV-1) infection. T-cell escape viral variants are retained following HIV-1 transmission between major histocompatibility complex (MHC)-matched individuals. However, reversion to wild type can occur following transmission to MHC-mismatched hosts in the absence of cytotoxic T-lymphocyte (CTL) pressure, due to the reduced fitness of the escape mutant virus. We estimated both the strength of immune selection and the fitness cost of escape variants by studying the rates of T-cell escape and reversion in pigtail macaques. Near-complete replacement of wild-type with T-cell escape viral variants at an immunodominant simian immunodeficiency virus Gag epitope KP9 occurred rapidly (over 7 days) following infection of pigtail macaques with SHIVSF162P3. Another challenge virus, SHIVmn229, previously serially passaged through pigtail macaques, contained a KP9 escape mutation in 40/44 clones sequenced from the challenge stock. When six KP9-responding animals were infected with this virus, the escape mutation was maintained. By contrast, in animals not responding to KP9, rapid reversion of the K165R mutation occurred over 2 weeks after infection. The rapidity of reversion to the wild-type sequence suggests a significant fitness cost of the T-cell escape mutant. Quantifying both the selection pressure exerted by CTL and the fitness costs of escape mutation has important implications for the development of CTL-based vaccine strategies.


Assuntos
Epitopos de Linfócito T/imunologia , Infecções por Lentivirus/imunologia , Infecções por Lentivirus/virologia , Lentivirus de Primatas , Vírus Reordenados , Linfócitos T Citotóxicos/imunologia , Animais , Mapeamento de Epitopos , Produtos do Gene gag/genética , Epitopos Imunodominantes , Lentivirus de Primatas/genética , Lentivirus de Primatas/patogenicidade , Macaca nemestrina , Mutação , Vírus Reordenados/genética , Vírus Reordenados/patogenicidade , Virulência
12.
Infect Genet Evol ; 5(3): 271-80, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15737919

RESUMO

The CC chemokine receptor 5 (CCR5) gene of primates encodes a transmembrane protein involved in cellular signaling of some cell types of the immune system. Numerous studies have shown that this peptide is used by lentiviruses in conjunction with the CD4 receptor to mediate binding and entry in target cells of human and non-human primates. New World monkeys (NWM), differently from their African counterparts, have no description of in natura lentivirus infection. Some evidences suggest that a blockage occurs at the viral entry step of infection. To investigate this possibility, we have cloned and sequenced CCR5 genes from several representatives of Platyrrhini, and compared their sequences with those of other Platyrrhini and Catarrhini species available at public databases. Platyrrhini CCR5 genes were shown to be more genetically diverse than their Catarrhini correlates, and their phylogenetic relationships based on that locus were in agreement with previous studies. Comparison of Platyrrhini and Catarrhini CCR5 consensus sequences evidenced several amino acid residues that differ between both groups, some of which have been experimentally associated with lentiviral interaction. A codon-based positive selection analysis showed that some of these sites seem to be under strong selection for variation among the Platyrrhini but not among Catarrhini species. These results suggest the potential involvement of those sites in the apparent refraction of some NWM to lentiviruses. The high ccr5 genetic diversity observed in Platyrrhini, however, argues for a more extensive infection analysis of diverse NWM species to evaluate this resistance and the potential use of those primates as HIV/AIDS animal models.


Assuntos
Cebidae/genética , Evolução Molecular , Infecções por Lentivirus/genética , Receptores CCR5/fisiologia , Adaptação Fisiológica/genética , Sequência de Aminoácidos , Animais , Predisposição Genética para Doença , Variação Genética , Lentivirus de Primatas/patogenicidade , Dados de Sequência Molecular , Filogenia , Receptores CCR5/genética , Homologia de Sequência de Aminoácidos
13.
J Virol ; 78(2): 1006-11, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14694132

RESUMO

Retrovirus tropism can be restricted by cellular factors such as Fv1, Ref1, and Lv1 that inhibit infection by targeting the incoming viral capsid. Here, we show that rodent cells exhibit differential sensitivity to infection by vesicular stomatitis virus G-pseudotyped lentiviruses and that differences between human immunodeficiency virus type 1 and simian immunodeficiency virus (SIVmac) infectivity are sometimes, but not always, governed by determinants in capsid-p2. In at least one case, resistance to SIVmac infection could be eliminated by saturation of target cells with noninfectious SIVmac particles. However, cross-saturation experiments and analysis of Fv1-null cells engineered to express natural or artificial Fv1 proteins revealed that lentivirus restriction in mouse cells is independent of Fv1. Overall, these findings indicate that novel restriction factors in rodents can modulate sensitivity to specific primate lentiviruses.


Assuntos
Capsídeo/metabolismo , Lentivirus de Primatas/fisiologia , Lentivirus de Primatas/patogenicidade , Roedores/virologia , Animais , Linhagem Celular , Proteínas de Fluorescência Verde , HIV-1/patogenicidade , HIV-1/fisiologia , HIV-2/patogenicidade , HIV-2/fisiologia , Humanos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos AKR , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Proteínas/metabolismo , Vírus da Imunodeficiência Símia/patogenicidade , Vírus da Imunodeficiência Símia/fisiologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo
14.
J Leukoc Biol ; 74(5): 683-90, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12960236

RESUMO

The unique capacity of dendritic cells (DCs) to capture and process pathogens for presentation to the immune system, combined with their capacity to express costimulatory and adhesion molecules as well as cytokines and chemokines, renders them powerful antigen-presenting cells. However, immunodeficiency viruses hijack DCs to facilitate virus dissemination while subverting effective immune activation. Depending on the activation level of the DC subset, human immunodeficiency virus can use different receptors (CD4, chemokine, and C-type lectin receptors) to bind to DCs. These aspects likely impact whether a DC is productively infected by or simply carries virus for transmission to more permissive targets. DCs efficiently transmit virus to CD4+ T cells, driving virus growth as well as providing signals to trigger virus expansion in virus-bearing CD4+ T cells. There is accumulating evidence that viral determinants (nef, tat) selectively modulate immature DC biology, fostering DC-T cell interactions and virus replication without up-regulating costimulatory molecules for effective immune function. In addition, virus-loaded, immature DCs activate CD4+ virus-specific T cells, and mature DCs stimulate CD4+ and CD8+ T cells. Thus, even if immature DCs entrap virus as it crosses the mucosae and initiate a CD4+ T cell response, this is likely insufficient to control infection. Appreciating how virus modulates DC function and what determines whether virus is processed for immune stimulation or transmitted between cells will unveil the exact role of these cells in the onset of infection and advance preventative microbicide and vaccine/therapeutic approaches.


Assuntos
Células Dendríticas/imunologia , Células Dendríticas/virologia , HIV/patogenicidade , Lentivirus de Primatas/patogenicidade , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , HIV/imunologia , Humanos , Linfócitos T/imunologia , Linfócitos T/virologia
15.
Mol Immunol ; 38(2-3): 241-7, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11532285

RESUMO

Since the first contact with the host, human immunodeficiency virus (HIV) exploits the complement system to reach maximal spread of infection. HIV has adapted many strategies to avoid complement-mediated lysis and uses the opsonization with complement fragments for attachment to complement receptors (CR). From the pathogen's perspective, binding to CR-expressing cells is remarkably beneficial, bringing together virus and activated target cells that are highly susceptible to infection. Moreover, complement-mediated trapping on CR+ cells permits HIV to infect surrounding cells even in the presence of an excess of neutralizing antibodies. Thus, complement activation initiates the assumption of power over the host's immune system by HIV and thus augments viral spread and replication throughout the body. On the other hand, natural hosts of primate lentiviruses, such as sooty mangabeys, African green monkeys and chimpanzees, are generally considered to be resistant to the development of AIDS, despite persistent viral replication. This review focuses on the possible link between the resistance to disease and species-specific diversity in function of human and monkey complement system.


Assuntos
Proteínas do Sistema Complemento , Infecções por HIV/imunologia , Lentivirus de Primatas/patogenicidade , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Animais , Infecções por HIV/etiologia , Haplorrinos , Humanos , Imunidade Inata , Síndrome de Imunodeficiência Adquirida dos Símios/etiologia , Especificidade da Espécie
16.
EMBO J ; 17(5): 1259-67, 1998 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-9482723

RESUMO

The primate immunodeficiency virus Vif proteins are essential for replication in appropriate cultured cell systems and, presumably, for the establishment of productive infections in vivo. We describe experiments that define patterns of complementation between human and simian immunodeficiency virus (HIV and SIV) Vif proteins and address the determinants that underlie functional specificity. Using human cells as virus producers, it was found that the HIV-1 Vif protein could modulate the infectivity of HIV-1 itself, HIV-2 and SIV isolated from African green monkeys (SIVAGM). In contrast, the Vif proteins of SIVAGM and SIV isolated from Sykes' monkeys (SIVSYK) were inactive for all HIV and SIV substrates in human cells even though, at least for the SIVAGM protein, robust activity could be demonstrated in cognate African green monkey cells. These observations suggest that species-specific interactions between Vif and virus-producing cells, as opposed to between Vif and virus components, may govern the functional consequences of Vif expression in terms of inducing virion infectivity. The finding that the replication of murine leukemia virus could also be stimulated by HIV-1 Vif expression in human cells further supported this notion. We speculate that species restrictions to Vif function may have contributed to primate immunodeficiency virus zoonosis.


Assuntos
Produtos do Gene vif/fisiologia , Lentivirus de Primatas/patogenicidade , Animais , Linhagem Celular , Células Cultivadas , Chlorocebus aethiops , Humanos , Infecções por Lentivirus/transmissão , Vírus da Leucemia Murina/fisiologia , Leucócitos Mononucleares , Especificidade da Espécie , Linfócitos T , Replicação Viral
18.
J Virol ; 70(4): 2516-24, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8642681

RESUMO

We previously reported that expression of human immunodeficiency virus type 1 strain NL4-3 (HIV-1(NL4-3))vpr causes cells to arrest in the G2 phase of the cell cycle. We examined the induction of cell cycle arrest by other HIV-1 isolates and by primary lentiviruses other than HIV-1. We demonstrate that the vpr genes from tissue culture-adapted or primary isolates of HIV-1 are capable of inducing G2 arrest. In addition, we demonstrate that induction of cell cycle arrest is a conserved function of members of two other groups of primate lentiviruses, HIV-2/simian immunodeficiency virus strain sm (SIVsm)/SIVmac and SIVagm. vpr from HIV-1, HIV-2, and SIVmac induced cell cycle arrest when transfected in human (HeLa) and monkey (CV-1) cells. vpx from HIV-2 and SIVmac did not induce detectable cell cycle arrest in either cell type, and SIVagm vpx was capable of inducing arrest in CV-1 but not HeLa cells. These results indicate that induction of cell cycle perturbation is a general property of lentiviruses that infect primates. The conservation of this viral function throughout evolution suggests that it plays a key role in virus-host relationships, and elucidation of its mechanism may reveal important clues about pathology induced by primary lentiviruses.


Assuntos
Ciclo Celular , Produtos do Gene vpr/fisiologia , Lentivirus de Primatas/fisiologia , Alelos , Sequência de Aminoácidos , Animais , Sequência de Bases , Western Blotting , Chlorocebus aethiops , DNA Viral , Fase G2 , Produtos do Gene vpr/genética , HIV-1/genética , HIV-1/fisiologia , HIV-2/genética , HIV-2/fisiologia , Células HeLa , Humanos , Lentivirus de Primatas/genética , Lentivirus de Primatas/patogenicidade , Dados de Sequência Molecular , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/fisiologia , Proteínas Virais Reguladoras e Acessórias/genética , Proteínas Virais Reguladoras e Acessórias/fisiologia , Produtos do Gene vpr do Vírus da Imunodeficiência Humana
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