| hippocampal neuronal loss in infant macaques orally infected with virulent simian immunodeficiency virus (siv). | the neurological impact of human immunodeficiency virus (hiv) on children includes loss of brain growth, motor abnormalities and cognitive dysfunction. despite early antiretroviral treatment (art) intervention to suppress viral load, neurological consequences of perinatal hiv-1 infection persist. utilizing the pediatric simian immunodeficiency virus (siv) infection model, we tested the hypothesis that early-life siv infection depletes neuronal population in the hippocampus. a total of 22 art-naï ... | 2017 | 28394273 |
| simian immunodeficiency virus sivmac239, but not sivmac316, binds and utilizes human cd4 more efficiently than rhesus cd4. | rhesus macaques are used to model human immunodeficiency virus type 1 (hiv-1) infections, but they are not natural hosts of hiv-1 or any simian immunodeficiency virus (siv). rather, they became infected with siv through cross-species transfer from sooty mangabeys in captivity. it has been shown that hiv-1 utilizes rhesus cd4 less efficiently than human cd4. however, the relative ability of siv envelope glycoproteins to bind or utilize these cd4 orthologs has not been reported. here we show that ... | 2017 | 28679752 |
| mauritian cynomolgus macaques with m3m4 mhc genotype control sivmac251 infection. | understanding natural hiv control may lead to new preventative or therapeutic strategies. several protective major histocompatibility complex (mhc) genotypes were found in humans and rhesus macaques. here, we report a simian immunodeficiency virus (siv) controller mhc genotype in mauritian cynomolgus macaques (mcms). | 2017 | 28748659 |
| translational research in the nonhuman primate model of tuberculosis. | infection with mycobacterium tuberculosis predominantly establishes subclinical latent infection over the lifetime of an individual, with a fraction of infected individuals rapidly progressing to active disease. the immune control in latent infection can be perturbed by comorbidities such as diabetes mellitus, obesity, smoking, and coinfection with helminthes or hiv. modeling the varying aspects of natural infection remains incomplete when using zebrafish and mice. however, the nonhuman primate ... | 2017 | 28575319 |
| [immune regulation effect of chinese medicine of invigorating spleen and kidney detoxification on simian immunodeficiency virus-infected rhesus macaque]. | to evaluate the effect of chinese medicine of invigorating spleen and kidney detoxification on simian immunodeficiency virus-infected rhesus macaque. eight siv rhesus macaques of the same age were randomly divided into chinese medicine of invigorating spleen and kidney detoxification group(hereinafter referred to as chinese medicine group) and anti-virus drug(haart) group. the traditional chinese medicine and antiviral therapy were given for 8 weeks, and peripheral blood was collected for detect ... | 2017 | 28822162 |
| pneumatosis intestinalis in an siv-infected rhesus macaque (macaca mulatta). | pneumatosis intestinalis (pi) has been described as an incidental finding in domestic animals and humans where it is associated with human immunodeficiency virus infection among other comorbidities. this report describes emphysematous changes consistent with pi in a simian immunodeficiency virus (siv)-infected rhesus macaque (macaca mulatta). | 2017 | 28809434 |
| a siv molecular clone that targets the cns and induces neuroaids in rhesus macaques. | despite effective control of plasma viremia with the use of combination antiretroviral therapies (cart), minor cognitive and motor disorders (mcmd) persist as a significant clinical problem in hiv-infected patients. non-human primate models are therefore required to study mechanisms of disease progression in the central nervous system (cns). we isolated a strain of simian immunodeficiency virus (siv), sivsm804e, which induces neuroaids in a high proportion of rhesus macaques and identified enhan ... | 2017 | 28787449 |
| dna prime/protein boost vaccination elicits robust humoral response in rhesus macaques using oligomeric simian immunodeficiency virus envelope and advax delta inulin adjuvant. | the partial success of the rv144 trial underscores the importance of envelope-specific antibody responses for an effective hiv-1 vaccine. oligomeric hiv-1 envelope proteins delivered with a potent adjuvant are expected to elicit strong antibody responses with broad neutralization specificity. to test this hypothesis, two siv envelope proteins were formulated with delta inulin-based adjuvant (advax) and used to immunize nonhuman primates. oligomeric gp140-gp145 from sivmac251 and sivsme660 was pu ... | 2017 | 28758637 |
| vaccine-induced immune responses against both gag and env improve control of simian immunodeficiency virus replication in rectally challenged rhesus macaques. | the ability to control lentivirus replication may be determined, in part, by the extent to which individual viral proteins are targeted by the immune system. consequently, defining the antigens that elicit the most protective immune responses may facilitate the design of effective hiv-1 vaccines. here we vaccinated four groups of rhesus macaques with a heterologous vector prime/boost/boost/boost (pbbb) regimen expressing the following simian immunodeficiency virus (siv) genes: env, gag, vif, rev ... | 2017 | 28732035 |
| early initiation of antiretroviral treatment postsiv infection does not resolve lymphoid tissue activation. | germinal center resident follicular helper t (tfh) cells in lymphoid follicles are a potential sanctuary for hiv/simian immunodeficiency virus (siv) replication. but the dynamics of germinal centers upon early initiation of antiretroviral therapy (art) and their potential role in the formation of viral sanctuaries post-siv infection are not fully understood. | 2017 | 28692537 |
| cytomegaloviral hypophysitis in a simian immunodeficiency virus-infected rhesus macaque (macacca mulatta). | rhesus macaques experimentally infected with simian immunodeficiency virus (siv) experience immunosuppression and often opportunistic infection. among the most common opportunistic infections are rhesus cytomegalovirus (rhcmv), a ubiquitous betaherpesvirus that undergoes continuous low-level replication in immunocompetent monkeys. upon siv-mediated immunodeficiency, rhcmv reactivates and results in lesions in numerous organ systems including the nervous and reproductive systems. we report the fi ... | 2017 | 28671330 |
| persistent accumulation of gut macrophages with impaired phagocytic function correlates with siv disease progression in macaques. | the contribution of macrophages in the gastrointestinal tract to disease control or progression in hiv infection remains unclear. to address this question, we analyzed cd163(+) macrophages in ileum and mesenteric lymph nodes (ln) from siv-infected rhesus macaques with dichotomous expression of controlling mhc class i alleles predicted to be siv controllers or progressors. infection induced accumulation of macrophages into gut mucosa in the acute phase that persisted in progressors but was resolv ... | 2017 | 28667761 |
| an intravaginal ring that releases three antiviral agents and a contraceptive blocks shiv-rt infection, reduces hsv-2 shedding, and suppresses hormonal cycling in rhesus macaques. | women globally need access to multipurpose prevention technologies (mpts) that prevent human immunodeficiency virus (hiv), sexually transmitted infections that increase hiv acquisition/transmission risk, and unintended pregnancy. seeking an mpt with activity against hiv, herpes simplex virus-2 (hsv-2), and human papillomavirus (hpv), we developed a prototype intravaginal ring (ivr), the mzcl ivr, which released the antiviral agents miv-150, zinc acetate, and carrageenan (mzc for short) and the c ... | 2017 | 28600625 |
| acute simian immunodeficiency virus infection triggers early and transient interleukin-7 production in the gut, leading to enhanced local chemokine expression and intestinal immune cell homing. | the intestinal barrier, one of the first targets of hiv/simian immunodeficiency virus (siv) is subjected to major physiological changes during acute infection. having previously shown that pharmaceutical injection of interleukin-7 (il-7) triggers chemokine expression in many organs leading to massive t-cell homing, in particular to the intestine, we here explored mucosal il-7 expression as part of the cytokine storm occurring during the acute phase of siv infection in rhesus macaques. quantifyin ... | 2017 | 28579989 |
| immunologic and virologic mechanisms for partial protection from intravenous challenge by an integration-defective siv vaccine. | the suppression of viral loads and identification of selection signatures in non-human primates after challenge are indicators for effective human immunodeficiency virus (hiv)/simian immunodeficiency virus (siv) vaccines. to mimic the protective immunity elicited by attenuated siv vaccines, we developed an integration-defective siv (idsiv) vaccine by inactivating integrase, mutating sequence motifs critical for integration, and inserting the cytomegalovirus (cmv) promoter for more efficient expr ... | 2017 | 28574482 |
| critical role for monocytes/macrophages in rapid progression to aids in pediatric simian immunodeficiency virus-infected rhesus macaques. | infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (hiv or siv), respectively, express higher viral loads and progress more rapidly to aids than infected adults. activated memory cd4(+) t cells in intestinal tissues are major primary target cells for siv/hiv infection, and massive depletion of these cells is considered a major cause of immunodeficiency. monocytes and macrophages are important cells of innate immunity and also are targets of hiv/siv infecti ... | 2017 | 28566378 |
| fibroblast-adapted human cmv vaccines elicit predominantly conventional cd8 t cell responses in humans. | cytomegalovirus (cmv)-based vaccines have shown remarkable efficacy in the rhesus macaque model of acquired immune deficiency syndrome, enabling 50% of vaccinated monkeys to clear a subsequent virulent simian immunodeficiency virus challenge. the protective vaccine elicited unconventional cd8 t cell responses that were entirely restricted by mhc ii or the nonclassical mhc i molecule, mhc-e. these unconventional responses were only elicited by a fibroblast-adapted rhesus cmv vector with limited t ... | 2017 | 28566275 |
| unusual antigen presentation offers new insight into hiv vaccine design. | recent findings with a rhesus monkey cytomegalovirus based simian immunodeficiency virus vaccine have identified strong cd8+ t cell responses that are restricted by mhc-e. also mycobacteria specific cd8+ t cells, that are mhc-e restricted, have been identified. mhc-e therefore can present a wide range of epitope peptides to cd8+ t cells, alongside its well defined role in presenting a conserved mhc-class i signal peptide to the nkg2a/c-cd94 receptor on natural killer cells. here we explore the a ... | 2017 | 28505602 |
| rare control of sivmac239 infection in a vaccinated rhesus macaque. | effector memory t cell (tem) responses display potent antiviral properties and have been linked to stringent control of simian immunodeficiency virus (siv) replication. since recurrent antigen stimulation drives the differentiation of cd8(+) t cells toward the tem phenotype, in this study we incorporated a persistent herpesviral vector into a heterologous prime/boost/boost vaccine approach to maximize the induction of tem responses. this new regimen resulted in cd8(+) tem-biased responses in fou ... | 2017 | 28503929 |
| the levels of dngr-1 and its ligand-bearing cells were altered after human and simian immunodeficiency virus infection. | dendritic cell nk lectin group receptor-1 (dngr-1), also known as c-type lectin domain family 9, member a (clec9a), is a member of c-type lectin receptor superfamily expressed primarily on dendritic cells (dc) that excel in cross-presentation of exogenous antigens. to find out whether and how it is affected in human immunodeficiency virus infections or acquired immunodeficiency syndromes (hiv/aids), dngr-1 expression and dngr-1-binding cells in simian/human immunodeficiency virus (shiv) and simi ... | 2017 | 28478499 |
| a lipopeptide hiv-1/2 fusion inhibitor with highly potent in vitro, ex vivo, and in vivo antiviral activity. | peptides derived from the c-terminal heptad repeat (chr) region of the human immunodeficiency virus type 1 (hiv-1) fusogenic protein gp41 are potent viral entry inhibitors, and currently, enfuvirtide (t-20) is the only one approved for clinical use; however, emerging drug resistance largely limits its efficacy. in this study, we generated a novel lipopeptide inhibitor, named lp-19, by integrating multiple design strategies, including an n-terminal m-t hook structure, an hiv-2 sequence, intraheli ... | 2017 | 28356533 |
| analysis of sivmac envelope-specific antibodies selected through phage display. | we have constructed a single chain fragment variable (scfv) phage display library from a simian immunodeficiency virus (siv)-infected rhesus macaque that developed unusually high-titer neutralizing antibody responses against tier-3, neutralization-resistant sivmac239. the library was screened using trimeric (gp140) and monomeric (gp120) forms of the sivmac239 envelope (env) glycoprotein. we also cloned variable-heavy and variable-light (vh-vl) antibody fragments from seven previously described r ... | 2017 | 28075174 |
| host and viral traits predict zoonotic spillover from mammals. | the majority of human emerging infectious diseases are zoonotic, with viruses that originate in wild mammals of particular concern (for example, hiv, ebola and sars). understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals for pandemic surveillance programs. however, few analytical tools exist to identify which host species are likely to harbour the next human virus, or which viruses can cross species ... | 2017 | 28636590 |