Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the first complete nucleotide sequence (8,440 base pairs) of a biologically active feline leukemia virus (FeLV), designated FeLV-61E (or F6A), and the molecular cloning, biological activity, and env-long terminal repeat (LTR) sequence of another FeLV isolate, FeLV-3281 (or F3A). F6A corresponds to the non-disease-specific common-form component of the immunodeficiency disease-inducing strain of FeLV, FeLV-FAIDS, and was isolated from tissue DNA of a cat following experimental transmission of naturally occurring feline acquired immunodeficiency syndrome. F3A clones were derived from a subgroup-A-virus-producing feline tumor cell line. Both are unusual relative to other molecularly cloned FeLVs studied to date in their ability to induce viremia in weanling (8-week-old) cats and in their failure to induce acute disease. The F6A provirus is organized into 5'-LTR-gag-pol-env-LTR-3' regions; the gag and pol open reading frames are separated by an amber codon, and env is in a different reading frame. The deduced extracellular glycoproteins of F6A, F3A, and the Glasgow-1 subgroup A isolate of FeLV (M. Stewart, M. Warnock, A. Wheeler, N. Wilkie, J. Mullins, D. Onions, and J. Neil, J. Virol. 58:825-834, 1986) are 98% homologous, despite having been isolated from naturally infected cats 6 to 13 years apart and from widely different geographic locations. As a group, their envelope gene sequences differ markedly from those of the disease-associated subgroup B and acutely pathogenic subgroup C viruses. Thus, F6A and F3A correspond to members of a highly conserved family and represent prototypes of the horizontally transmitted, minimally pathogenic FeLV present in all naturally occurring infections.
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PMID:Strong sequence conservation among horizontally transmissible, minimally pathogenic feline leukemia viruses. 282 67

The pandemic of HIV/AIDS consists of multiple foci with distinct epidemiological characteristics. Among the approximately one million Southeast Asians infected with HIV, subtype (clade) E infections predominate. This subtype, a recombinant virus comprised of a clade A core (gag) gene and a mosaic clade A/clade E envelope (env) gene, became broadly epidemic in Thailand beginning in 1989. Since then, subtype E HIV has become increasingly prevalent throughout Southeast Asia. Consistent with the recent introduction of clade E HIV, the diversity of Southeast Asian subtype E viruses is narrow (6% nucleotide diversity across env). Since neutralizing antibodies may play a protective role against HIV infection, and are relatively clade specific for genotype E viruses, a subtype E-derived candidate vaccine tested in Southeast Asia would provide an optimal test of vaccine concept. It would also provide, for the first time to a developing region of the world, a non-B clade candidate vaccine designed specifically for the local epidemic. A consortium of industry (Chiron Vaccines and Pasteur Merieux Connaught), academic (Mahidol and Chiang Mai Universities) and military (United States and Royal Thai Army Medical Departments) medicine is working together to develop and test HIV vaccines for the genotype E epidemic. A genotype B recombinant glycoprotein (rgp)120 candidate vaccine has undergone phase I/II testing in Thailand and confirmed to be safe and immunogenic in this ethnic group. An rgp120 (E) has been produced and a phase I/II trial of the bivalent product (B/E) is in the final stages of approval. This vaccine construct is designed to elicit humoral immune responses. To augment these antibody responses with CD8+ CTL responses, an E-specific, live-vectored vaccine is being developed which will be used in conjunction with rgp120 in a second vaccine approach. Canarypox (ALVAC) constructs containing multiple HIV genes (gag/pol/env) currently designed for the subtype B epidemics will be modified to contain a clade E env gene sequence. After predetermined milestones have been met, these two subtype E-specific candidate vaccines will be assessed for protection in a large collaborative efficacy trial. Since neither animal models nor laboratory assays are validated as predictive of HIV vaccine efficacy, it must be through such a phase III trial that vaccine-induced protection and immunologic correlates will be determined.
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PMID:HIV vaccine development: a subtype E-specific strategy. 988 32

Simian retroviruses (SRVs), the etiological agent of a spontaneous Simian acquired immunodeficiency syndrome, endemically infects large percentages of Asian macaques housed in biomedical research colonies and severely compromises the effective use of these species as a viable research animal. We recently described the molecular cloning of a serogroup 2 SRV, D2/RHE/OR, which causes mild immunosuppression in rhesus macaques. A restriction site variant, D2/RHE/OR/V1, has also been recovered from severely ill animals endemically infected with D2/RHE/OR. We now report the complete nucleotide sequences of D2/RHE/OR and D2/RHE/OR/V1. Both infectious molecular clones retain the genetic structure typical of type D SRVs (5' LTR-gag-prt-pol-env-3'LTR) and encode identically sized 8105-bp proviruses. D2/RHE/OR and D2/RHE/OR/V1 are 99.3% similar at the amino acid level, exhibiting only 17 residue differences, of which 10 are located in the envelope glycoproteins. The molecular clones and reciprocal chimeric viruses were used to assess the contribution of different genetic domains to virus infectivity in a T cell infection assay. These experiments indicate that D2/RHE/OR has a reduced ability to infect specific T cell lines, especially Hut-78 and MT-4 cells, and that the envelope gene is not the sole determinant of in vitro tropism.
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PMID:Molecular cloning and cell-specific growth characterization of polymorphic variants of type D serogroup 2 simian retroviruses. 1044 55

Prior studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high levels of viremia and AIDS following challenge with a pathogenic strain of SIV (V. M. Hirsch et al., J. Virol. 70:3741-3752, 1996). This MVA-SIV recombinant expressed relatively low levels of the Gag-Pol portion of the vaccine. To optimize protection, second-generation recombinant MVAs that expressed high levels of either Gag-Pol (MVA-gag-pol) or Env (MVA-env), alone or in combination (MVA-gag-pol-env), were generated. A cohort of 24 macaques was immunized with recombinant or nonrecombinant MVA (four groups of six animals) and was challenged with 50 times the dose at which 50% of macaques are infected with uncloned pathogenic SIVsmE660. Although all animals became infected postchallenge, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines as compared with animals that received nonrecombinant MVA (P = 0.0011 by repeated-measures analysis of variance). The differences in the degree of virus suppression achieved by the three MVA-SIV vaccines were not significant. Most importantly, the reduction in levels of viremia resulted in a significant increase in median (P < 0.05 by Student's t test) and cumulative (P = 0.010 by log rank test) survival. These results suggest that recombinant MVA has considerable potential as a vaccine vector for human AIDS.
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PMID:Comparative efficacy of recombinant modified vaccinia virus Ankara expressing simian immunodeficiency virus (SIV) Gag-Pol and/or Env in macaques challenged with pathogenic SIV. 1068 90

Neutralizing antibodies were assessed before and after intravenous challenge with pathogenic SIVsmE660 in rhesus macaques that had been immunized with recombinant modified vaccinia virus Ankara expressing one or more simian immunodeficiency virus gene products (MVA-SIV). Animals received either MVA-gag-pol, MVA-env, MVA-gag-pol-env, or nonrecombinant MVA. Although no animals were completely protected from infection with SIV, animals immunized with recombinant MVA-SIV vaccines had lower virus loads and prolonged survival relative to control animals that received nonrecombinant MVA (I. Ourmanov et al., J. Virol. 74:2740-2751, 2000). Titers of neutralizing antibodies measured with the vaccine strain SIVsmH-4 were low in the MVA-env and MVA-gag-pol-env groups of animals and were undetectable in the MVA-gag-pol and nonrecombinant MVA groups of animals on the day of challenge (4 weeks after final immunization). Titers of SIVsmH-4-neutralizing antibodies remained unchanged 1 week later but increased approximately 100-fold 2 weeks postchallenge in the MVA-env and MVA-gag-pol-env groups while the titers remained low or undetectable in the MVA-gag-pol and nonrecombinant MVA groups. This anamnestic neutralizing antibody response was also detected with T-cell-line-adapted stocks of SIVmac251 and SIV/DeltaB670 but not with SIVmac239, as this latter virus resisted neutralization. Most animals in each group had high titers of SIVsmH-4-neutralizing antibodies 8 weeks postchallenge. Titers of neutralizing antibodies were low or undetectable until about 12 weeks of infection in all groups of animals and showed little or no evidence of an anamnestic response when measured with SIVsmE660. The results indicate that recombinant MVA is a promising vector to use to prime for an anamnestic neutralizing antibody response following infection with primate lentiviruses that cause AIDS. However, the Env component of the present vaccine needs improvement in order to target a broad spectrum of viral variants, including those that resemble primary isolates.
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PMID:Recombinant modified vaccinia virus ankara expressing the surface gp120 of simian immunodeficiency virus (SIV) primes for a rapid neutralizing antibody response to SIV infection in macaques. 1068 19

Since virus-specific CTL play a central role in containing HIV replication, a candidate AIDS vaccine should generate virus-specific CTL responses. In this study, the ability of a recombinant canarypox virus expressing SIV Gag-Pol-Env (ALVAC/SIV gag-pol-env) was assessed for its ability to elicit both dominant and subdominant epitope-specific CTL responses in rhesus monkeys. Following a series of five immunizations, memory CTL responses specific for a dominant Gag epitope could be demonstrated in the peripheral blood of vaccinated monkeys. Memory CTL responses to a subdominant Pol epitope were undetectable in these animals. Following challenge with SIVmac251, the experimentally vaccinated animals developed high frequency CTL responses specific for the dominant Gag epitope that emerged in temporal association with the early containment of viral replication. Interestingly, the experimentally vaccinated, but not the control vaccinated animals, developed CTL responses to the subdominant Pol epitope that were detectable only after containment of early viremia. Thus, recombinant canarypox vaccination elicited low frequency, but durable memory CTL populations. The temporal association of the emergence of the dominant epitope-specific response with early viral containment following challenge suggests that this immune response played a role in the accelerated clearing of early viremia in these animals. The later emerging CTL response specific for the subdominant epitope may contribute to the control of viral replication in the setting of chronic infection.
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PMID:Recombinant canarypox vaccine-elicited CTL specific for dominant and subdominant simian immunodeficiency virus epitopes in rhesus monkeys. 1182 18

Forty-one HIV-1 strains from Gabonese patients were studied according to the following strategy: nested polymerase chain reaction were performed to obtain an approximately 1,100-bp fragment containing the protease gene and the 5' half of the reverse transcriptase gene. Additional amplifications were carried out to obtain an approximately 700-bp fragment encompassing the C2V3 env gene. Fragments of 600 to 1,200 bp in the gag gene overlapping the pol sequences were used for the study of recombination patterns. Phylogenetic analyses of the different fragments were used to investigate HIV-1 diversity in Gabon. Thirty-one strains were sequenced in the env and pol genes and phylogenetic analyses classified them as subtype A (n = 2), D (n = 4), G (n = 1), H (n = 1), CRF02 (n = 8), and CRF MAL-like (n = 6); in addition, there were 6 unique recombinant forms and 1 unclassified strain, and in 2 cases pol/env sequences classified strains as subtype D whereas gag phylogeny classified them as subtype A. In 10 cases only 1 fragment was available: 4 env (2 subtype D, 1 subtype H, and 1 subtype U) and 6 pol (1 subtype A, 1 subtype C, 2 subtype G, and 2 subtype U). Minor mutations associated with viral resistance to antiretroviral drugs were observed in more than 80% of analyzed strains. Our study confirms the extensive HIV-1 diversity found in Central Africa, with more than 70% of strains from Gabon exhibiting discordant clustering in pol and env genomic regions and less than 60% concordance between sequencing and heteroduplex mobility assay genotyping. These findings highlight the fact that Central Africa represents the epicenter for the origin of HIV-1. The strategy of sequencing pol in association with env has proved to be useful for analysis of the recombinant strains. The main advantage of this approach is that it also allows for evaluation of genotypic susceptibility to antiretroviral drugs without the need for supplementary analyses.
AIDS Res Hum Retroviruses 2002 Oct 10
PMID:Analysis of partial pol and env sequences indicates a high prevalence of HIV type 1 recombinant strains circulating in Gabon. 1239 49

To investigate the route of zoonotic transmission of HIV-1, we isolated three and seven HIV-1 strains from 449 Pygmy hunter gatherers and 169 neighboring Bantu, respectively, in southern Cameroon. Phylogenetic analysis based on pol-integrase and env-C2V3 sequences revealed that strains from Pygmies were 1CRF02_AG/CRF02_AG, 1 subtype G/CRF02 AG (pol/env), and 1 CRFll_cpx/CRF11_cpx, and that those from Bantu were 2 CRF02_AG/CRF02_AG, 1 CRF02_AG/CRF01_AE/A, 1 CRF02_AG/subtype A, 1 G/A, 1G/CRF02_AG, and 1 unclassified fH. CRF02_AG and CRF11_cpx have been identified in Cameroon. The results suggest that HIV-1 has been introduced into Pygmies through their neighboring Bantu rather than directly from nonhuman primates.
AIDS Res Hum Retroviruses 2003 May
PMID:HIV type 1 infection in Pygmy hunter gatherers is from contact with Bantu rather than from nonhuman primates. 1281 89

To investigate the prevalence of subtypes A and C, and the existence of recombinants of both subtypes in the southeast of the Democratic Republic of Congo (DRC), blood samples were collected from 27 HIV-infected individuals in Likasi, located in an area bordering close to Zambia, and analyzed phylogenetically. Out of the 24 strains with a positive PCR profile for pol-IN and env-C2V3, 15 (62.5%) had a discordant subtype or CRF designation: one subtype A/G (pol/env), four A/U (unclassified), three G/A, one G/CRF01, three H/A, one J/C, one CRF02 (G)/A, and one U/A. Nine (37.5%) strains had a concordant subtype or CRF designation: five subtype A, two C, one D, and one CRF02/G. The remaining three samples negative for PCR with env-C2V3 primers used in this study were further analyzed with env-gp41 primers and revealed the presence of two profiles: two J/J (pol-IN/env-gp41) and one C/G. These data highlight the presence of a high proportion (16/27, 59.3%) of recombinant strains and a low prevalence (4.1 and 7.4%) of subtype C based on env-C2V3 and pol-IN analyses, respectively, in Likasi. In addition, this is the first report that CRF02_AG exists in DRC, though the epidemiological significance of the existence of CRF02_AG in DRC remains unknown.
AIDS Res Hum Retroviruses 2004 Dec
PMID:Genetic diversity of HIV type 1 in Likasi, southeast of the Democratic Republic of Congo. 1565 Apr 28

Southern Brazil has the highest prevalence rate of AIDS in the country and is the only region in the Americas where HIV-1 C prevails. Metropolitan areas and harbor cities have been evaluated, but limited information is available for small towns and specific populations. We studied women attending the obstetric outpatient clinic of Criciuma, State of Santa Catarina in 2007 to evaluate the molecular epidemiology of HIV-1 among pregnant women living with HIV/AIDS. Forty-two cases had partial pol gene sequenced and additional partial gag and/or env genes from nine women. HIV subtyping was evaluated by phylogenetic methods and antiretroviral (ARV) drug resistance mutations (DRMs) at the Stanford Database. DRMs to one or more ARV class was observed in 20/42, 48% of cases, with 15/41, 37% with viral load <500 copies/ml. Subtype C at pol was identified in 33/42, 78.6% (95% CI: 64-89%), C mosaics (CB, CF) in 2, 4.8% (95% CI: 0.8-19%), F in 4, 9.5% (95% CI: 3-21%), and B in 3, 7.1% (95% CI: 1.8-18%). Discordance in concatenated gag/pol/env or intraregion mosaic was observed in 1/9, 11% of HIV-1 C genomes. The proportion of HIV-1 C in this study is the highest rate described in the Americas. Molecular surveillance in specific populations is instrumental for a better understanding of the Brazilian HIV epidemic.
AIDS Res Hum Retroviruses 2010 Mar
PMID:Young pregnant women living with HIV/AIDS in Criciuma, Southern Brazil, are infected almost exclusively with HIV type 1 clade C. 2033 70


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