Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus (HIV) infection leads to a decline of CD4+ T-cells in blood. Because blood represents only a small proportion of the total lymphocyte pool, it is important to investigate other lymphoid organs. So far, only relative proportions of lymphocyte subsets in single peripheral lymph node (LN) regions of HIV-infected patients and simian immunodeficiency virus (SIV)-infected macaques have been documented. We have therefore quantified the absolute numbers of lymphocyte subsets in blood and six different LN regions of 10 uninfected and 26 SIV-infected macaques. In addition, we have determined the expression of markers of activation and differentiation. Already, in uninfected monkeys, there were significant differences in the cellular composition of different LN regions. Infection with SIV resulted in drastic changes in the proportion as well as absolute numbers of different lymphocyte subsets. Moreover, the relative contribution of the single LN regions to the total lymphocyte pool was also altered.
J Med Primatol 2000 Aug
PMID:Total numbers of lymphocyte subsets in different lymph node regions of uninfected and SIV-infected macaques. 1108 77

Thus far, simian immunodeficiency virus from chimpanzees (SIVcpz) genomes have been characterized as Pan troglodytes troglodytes and show a strong relation with human immunodeficiency virus (HIV)-1 N in their env genes. We fully characterized another SIVcpz from P. t. troglodytes. This chimpanzee (Cam5) was, as was also the host of SIVcpz-cam3, wild born in Cameroon, a region where all three groups of HIV-1 (M, N and O) co-occur. In contrast to other SIVcpz, SIVcpz-cam5 was isolated immediately after the rescue of the animal. Our data demonstrate that SIVcpz-cam5, like SIVcpz-cam3, grows easily on human peripheral blood mononuclear cells (PBMCs) and uses CCR5 as a co-receptor similar to HIV-1 N YBF30. Phylogenetic analysis based on the entire env gene shows that SIVcpz-cam5 falls into the same unique subcluster as HIV-1 N YBF30, SIVcpz-cam3 and SIVcpz-US. A phylogenetic relationship was also found with the vif gene of HIV-1 N. This study provides proof that HIV-1 N related viruses circulate in wild P. t. troglodytes.
J Med Primatol 2000 Aug
PMID:SIVcpz from a naturally infected Cameroonian chimpanzee: biological and genetic comparison with HIV-1 N. 1108 79

We previously reported major histocompatibility complex Class I-restricted cytotoxic T lymphocytes (CTL) in jejunal lamina propria (LP) of monkeys following colonic exposure to subinfectious SIV doses. Those monkeys with strong mucosal CTL responses specific for simian immunodeficiency virus (SIV) envelope (env) were protected from later colonic challenge with a heterologous pathogenic virus dose. Here, env-specific CTL were similarly induced in jejunal LP in five of eight non-progesterone treated macaques that were vaginally exposed to SIV, but not infected. Subsequent vaginal challenge following progesterone treatment produced systemic infection. The only two monkeys that had jejunal env-specific CTL detectable post-challenge developed significantly lower plasma virus loads, and had delayed disease progression. Either vaginal or colonic exposure to subinfectious SIV doses can induce CTL detectable in jejunal LP. The association of such CTL with protection or delayed disease upon challenge suggests that successful vaccine protection against SIV/HIV may require CTL responses in the mucosa.
J Med Primatol 2000 Aug
PMID:Identification of SIV env-specific CTL in the jejunal mucosa in vaginally exposed, seronegative rhesus macaques (Macaca mulatta). 1108 80

The Tat protein of human immunodeficiency virus (HIV) is produced very early after infection, plays a key role in the virus life cycle and in acquired immunodeficiency syndrome (AIDS) pathogenesis, is immunogenic and well conserved among all virus clades. Notably, a Tat-specific immune response correlates with non-progression to AIDS. Here, we show that a vaccine based on the Tat protein of HIV blocks primary infection with the simian/human immunodeficiency virus (SHIV)89.6P and prevents the CD4 T cell decline and disease onset in cynomolgus monkeys. No signs of virus replication were found in five out of seven vaccinated macaques for almost 1 year of follow-up. Since the inoculated virus (derived from rhesus or from cynomolgus macaques) is shown to be highly pathogenic in cynomolgus macaques, the results indicate efficacy of Tat vaccination in protection against highly pathogenic virus challenge. Finally, the studies of the Tat-specific immunological responses indicate a correlation of protection with a cytotoxic T cell response. Thus, a Tat-based vaccine is a promising candidate for preventive and therapeutic vaccination in humans.
J Med Primatol 2000 Aug
PMID:SHIV89.6P pathogenicity in cynomolgus monkeys and control of viral replication and disease onset by human immunodeficiency virus type 1 Tat vaccine. 1108 82

A simian immunodeficiency virus (SIV)(Mne) DNA clone was constructed that produces viruses containing a four amino acid deletion in the second zinc finger of the nucleocapsid (NC) domain of the Gag polyprotein. Viruses produced from this clone, although non-infectious both in vitro and in vivo, complete a majority of the steps in a single retroviral infection cycle. Eight pig-tailed macaques (Macaca nemestrina) were inoculated intramuscularly and subcutaneously three times over the course of 24 weeks with the NC mutant expressing DNA. These macaques, and four controls, were then challenged mucosally (intrarectally) with the homologous virus (SIV Mne CL E11S) and monitored for evidence of infection and clinical disease. Prior to challenge, a measurable humoral immune response was noted in four of eight immunized macaques. After challenge, all 12 macaques became infected, although four immunized animals greatly restricted their viral replication, and one immunized animal that controlled replication remains antibody negative. No disease has been evidence during the 46-week period of monitoring after challenge.
J Med Primatol 2000 Aug
PMID:Mucosal challenge of Macaca nemestrina with simian immunodeficiency virus (SIV) following SIV nucleocapsid mutant DNA vaccination. 1108 83

We have previously used a panel of quantitative and qualitative serological assays to define a lengthy and complex maturation of envelope-specific antibody responses in monkeys experimentally infected with attenuated simian immunodeficiency virus (SIV) that is closely associated with the temporal development of enduring and protective immunity to experimental virus challenge. To elucidate in more detail the changes in antibody specificity associated with this maturation, we describe here 'domain-specific' serological studies to characterize the evolution of antibody responses to defined linear determinants of the SIV envelope protein. The results of these studies reveal for the first time distinguishing differences in the evolution of antibody populations to distinct envelope peptide segments, as determined by measurements of antibody titer and avidity, indicating different patterns of antibody maturation to distinct linear envelope antigenic determinants. Thus, these data demonstrate the potential for domain-specific serology to produce a high-resolution characterization of SIV-specific antibody responses that can be used to evaluate experimental vaccine responses and to identify potential immune correlates of protection.
J Med Primatol 2000 Aug
PMID:Maturation of envelope-specific antibody responses to linear determinants in monkeys inoculated with attenuated SIV. 1108 84

The only vaccines shown to be protective against intravenous challenge with virulent virus in the simian immunodeficiency virus (SIV)/macaque model are attenuated live SIVs. However, these vaccines have several disadvantages: 1) they persist indefinitely in vaccinated macaques; 2) they are pathogenic to neonatal macaques; and 3) they are lethal in some adult macaques. To enhance the safety and efficacy of these vaccines, we immunized macaques first with recombinant vaccines and then inoculated the animals with SIV(delta(nef)). In the first experiment, preimmunized macaques advanced to disease slower than controls after challenge with virulent SIV; five animals survived for 3 years without disease and only the vaccine virus (SIV(delta(nef)) could be isolated at this time. In the second experiment, preimmunized animals had lower virus loads and no disease compared to controls.
J Med Primatol 2000 Aug
PMID:Enhanced safety and efficacy of live attenuated SIV vaccines by prevaccination with recombinant vaccines. 1108 85

We report that simian immunodeficiency virus (SIV) infection in macaques is a valuable animal model for studying post-exposure chemoprophylaxis (PECP). PECP with the acyclic nucleoside reverse transcriptase inhibitors 9-(2-phosphonylmetho-xyethyl)adenine (PMEA) and (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) at early viral infection can provide long-term protection against subsequent heterologous SIV challenge. Eight macaques previously treated with PECP (called PECP macaques) and four naive controls were challenged intravenously with the most virulent form of SIV, SIV(PBj14). All controls showed signs of SIV(PBj14)-induced acute disease syndrome on days 6 and 7 post-inoculation (PI). One had a fatal viral infection and two surviving controls had persistent infection and decreased CD4+ cell count. Virologic studies of the three surviving controls revealed SIV in multiple lymphoid tissues and peripheral blood mononuclear cells (PBMCs) at necropsy. In contrast, the PECP macaques showed none to mild signs of acute disease syndrome at day 9 PI and exhibited only transient SIV infection in PBMCs between weeks 1 and 8 PI. In virologic studies of five PECP macaques necropsied, two macaques were SIV-negative and the other three were SIV-positive only in either lymph node or bone marrow. Three SIV(PBj14)-challenged PECP macaques, that were randomly reserved for a follow-up study for > 4.0 years PI showed extremely low to undetectable levels of PBMC-associated viremia and normal to increased levels of CD4 + and CD8 + cell counts throughout the study. Our results indicate that early PECP could activate immune responses to protect against subsequent infection with heterologous challenge virus.
J Med Primatol 2000 Aug
PMID:Post-exposure chemoprophylaxis (PECP) against SIV infection of macaques as a model for protection from HIV infection. 1108 87

Groups of rhesus monkeys were inoculated with: 1) simian immunodeficiency virus (SIV)B670 alone; 2) Mycobacterium leprae alone; 3) SIV plus M. leprae on the same day; and 4) M. leprae 2 weeks after SIV. Animals were monitored at intervals for virus loads, antibody responses to M. leprae glycolipid antigens and to SIV Gp120, T-cell CD4+ and CD4+ CD29+ subset percentages, leprosy and acquired immunodeficiency syndrome (AIDS) clinical symptoms. Five out of six animals developed leprosy in each co-inoculated group, compared to one out of six in the M. leprae-only-inoculated group, indicating that M. leprae/SIV co-infection increases the susceptibility to leprosy, regardless of the timing of the two infections. Animals in the co-infected group that received M. leprae 2 weeks after SIV had a significantly slower rate of AIDS progression and long-term survival was significantly greater (three out of six) compared to the group inoculated with SIV alone (zero out of seven). All M. leprae-only-inoculated animals (six out of six) survived. Post-SIV-inoculation, a rapid decrease in the percentages of CD4 + and CD4 + CD29 + T-cells was observed in the SIV-only-inoculated group that was significantly blocked by co-inoculation with M. leprae 2 weeks after SIV, but not by SIV on the same day. The virus load set point was increased by approximately two logs in the group inoculated with M. leprae and SIV on the same day compared to SIV 2 weeks prior to M. leprae or the SIV-only-inoculated group. The results indicate that M. leprae, inoculated 2 weeks after SIV, decreased the pathogenicity of SIV compared to inoculation of M. leprae and SIV on the same day or SIV alone. The decreased pathogenicity correlated with a diminished loss of CD4 + and CD4 + CD29 + T-cell subsets in the group inoculated with M. leprae 2 weeks after SIV compared to the group inoculated with SIV alone. IgG antibody responses to M. leprae-specific cell wall phenolic glycolipid-I antigen were inhibited by 2-week-prior or same-day SIV co-inoculation compared to M. leprae-only inoculated animals. The IgG anti-lipoarabinomannan antibody response was enhanced in the group inoculated with M. leprae and SIV on the same day compared to the groups inoculated with M. leprae alone or SIV 2 weeks prior to M. leprae. Antibody responses to SIV Gp120 antigen were unimpaired in both co-inoculated groups compared to SIV-only-inoculated groups. The antibody results show that the immune responses to SIV and M. leprae are interrelated in SIV/M. leprae co-infected animals.
J Med Primatol 2000 Aug
PMID:Interactions between Mycobacterium leprae and simian immunodeficiency virus (SIV) in rhesus monkeys. 1108 88

Following DNA immunization of rhesus macaques with a plasmid encoding the human immunodeficiency virus (HIV)-1 third variable domain (V3) loop, presented by pseudo-viral envelope particles of hepatitis B virus, specific immune responses were induced. The primates were then inoculated with a chimeric simian/human immunodeficiency virus (SHIV). All the animals were infected, but the V3-specific immunization provided a relative attenuation of the acute phase of infection in the absence of neutralizing antibody. In all animals, SHIV-specific cytotoxic T-lymphocyte precursors (CTLp) were detected early in peripheral blood and lymph nodes. The viremia peak correlated significantly with the decrease in CD4+ T cells and with a transient increase in the percentage of natural killer cells. The infection induced an oligoclonalization of the CD8+ T-cell variable beta chain repertoire in the blood. Surprisingly, HIV envelope-specific CTLp generated by genetic immunization may be governed by distinct circulation rules compared to SHIV-specific CTLp induced by infection.
J Med Primatol 2000 Dec
PMID:Immune responses following simian/human immunodeficiency virus (SHIV) challenge of rhesus macaques after human immunodeficiency virus (HIV)-1 third variable domain (V3) loop-based genetic immunization. 1116 28


<< Previous 1 2 3 4 5 6 7 8 9 10