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1.
J Virol ; 75(23): 11417-25, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11689623

RESUMO

Human immunodeficiency virus type 1 (HIV-1) subtype C is responsible for more than 56% of all infections in the HIV and AIDS pandemic. It is the predominant subtype in the rapidly expanding epidemic in southern Africa. To develop a relevant model that would facilitate studies of transmission, pathogenesis, and vaccine development for this subtype, we generated SHIV(MJ4), a simian/human immunodeficiency virus (SHIV) chimera based on HIV-1 subtype C. SHIV(MJ4) contains the majority of env, the entire second exon of tat, and a partial sequence of the second exon of rev, all derived from a CCR5-tropic, primary isolate envelope clone from southern Africa. SHIV(MJ4) replicated efficiently in human, rhesus, and pig-tailed macaque peripheral blood mononuclear cells (PBMCs) in vitro but not in CEMx174 cells. To assess in vivo infectivity, SHIV(MJ4) was intravenously inoculated into four rhesus macaques (Macaca mulatta). All four animals became infected as determined through virus isolation, PCR analysis, and viral loads of 10(7) to 10(8) copies of viral RNA per ml of plasma during the primary infection phase. We have established a CCR5-tropic SHIV(MJ4)/rhesus macaque model that may be useful in the studies of HIV-1 subtype C immunology and biology and may also facilitate the evaluation of vaccines to control the spread of HIV-1 subtype C in southern Africa and elsewhere.


Assuntos
HIV-1/patogenicidade , Modelos Biológicos , Vírus da Imunodeficiência Símia/patogenicidade , Sequência de Aminoácidos , Animais , Formação de Anticorpos , Sequência de Bases , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/citologia , Linhagem Celular , Quimera , Primers do DNA , HIV-1/genética , HIV-1/imunologia , HIV-1/fisiologia , Humanos , Macaca mulatta , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/imunologia , Vírus da Imunodeficiência Símia/fisiologia , Carga Viral , Replicação Viral
2.
Virology ; 287(2): 261-5, 2001 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-11531404

RESUMO

Multiple subtypes of HIV-1 have been identified; however, there is little data on the relative transmissibility of viruses belonging to different subtypes. A matched case-control study addressed whether viruses with different long terminal repeat (LTR) subtypes were transmitted equally from mother to infant. The LTR subtype was determined for 45 matched cases and controls who participated in a clinical trial in Tanzania. HIV-1 subtypes A, C, and D and intersubtype recombinant sequences were identified. Exact matched logistic regression analysis showed that viruses containing subtype A or intersubtype recombinant LTRs were 3.2 and 4.8 times more likely to be transmitted from mother to infant than viruses with subtype D LTRs. Viruses containing subtype C LTRs were 6.1 times more likely to be transmitted than those with subtype D LTRs. These differences in transmission were independent of maternal CD4 at enrollment. Thus, it appears that HIV-1 subtype may be associated with differing rates of perinatal transmission in Tanzania.


Assuntos
Infecções por HIV/transmissão , Repetição Terminal Longa de HIV/genética , HIV-1/fisiologia , Feminino , Feto/virologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Humanos , Gravidez , Recombinação Genética
3.
AIDS ; 15(9): 1157-65, 2001 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-11416718

RESUMO

OBJECTIVE: To examine predictors of vertical transmission of HIV-1 in Dar-es-Salaam, Tanzania. DESIGN: Observational design. METHODS: Consenting HIV-1-infected pregnant women (n = 1078) were enrolled in a trial to examine the role of vitamin supplements. Intrauterine HIV-1 infection (HIV-positive at birth); intrapartum and early breastfeeding transmission (HIV-positive at 6 weeks among those uninfected at birth) were defined using the PCR. RESULTS: Of 734 infants who had a specimen taken at birth, 62 were HIV positive [8.4%; 95% confidence interval (CI),6.4--10.5%], whereas 59 infants were positive among 367 infants who were uninfected at birth and were retested at 6 weeks (16.1%; 95%CI, 12.3--19.8%). In multivariate analyses, maternal CD4 cell count, viral load, and clinical stage were significant predictors of both definitions of transmission. Viral load of 50 000 copies/ml or more at delivery was associated with a 4.21-fold increase in risk of intrapartum and early breastfeeding transmission (95%CI, 1.59--11.13;P = 0.004). Babies who were HIV negative at birth and born before 34 weeks of gestation were 2.19 times more likely to become infected during intrapartum and early breastfeeding periods compared with those born after 37 weeks (95%CI, 1.19--4.04; P = 0.01). Gonorrhea at baseline was related to intrauterine transmission [multivariate risk ratio (RR), 5.50; 95%CI, 2.04--14.81; P < 0.001] but not intrapartum and early breastfeeding transmission. Signs of lower genital infections at or after enrollment were also associated with transmission. CONCLUSIONS: Reducing prematurity, rate of HIV disease progression, and maternal viral load at or after delivery could help to reduce vertical transmission. Treatment of sexually transmitted infections at onset of prenatal care, about 20 weeks on average, was inadequate for prevention of transmission. Whether sustained clearance of lower genital tract infections result in reduced transmission remains to be determined.


Assuntos
Infecções por HIV/transmissão , HIV-1 , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez , Adulto , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/imunologia , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , RNA Viral/sangue , Tanzânia , Útero , Carga Viral
4.
J Virol ; 75(11): 4964-72, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11333875

RESUMO

Human immunodeficiency virus type 1 (HIV-1) subtype C is now the predominant subtype in the global epidemic. This subtype is encountered in southern Africa and parts of Asia, where the epidemic is rapidly spreading. One possible explanation for these epidemiological observations is that this subtype has genetic characteristics that may contribute to its spread and/or pathogenic potential. In this report, we describe the construction of MJ4, an infectious chimeric molecular clone of HIV-1 subtype C that replicates in donor peripheral blood mononuclear cells and macrophages. We also tested this clone for its ability to use the chemokine receptors CCR1, CCR2b, CCR3, CXCR4, and CCR5 and found that the clone utilizes only CCR5 as the coreceptor for cell entry. The MJ4 clone will be useful in further biological and virological characterization of HIV-1 subtype C and will be an important tool in the continuing efforts to understand what may constitute protective immunity in HIV-1. The clone may also be used in experimental design of vaccine candidates that may be directed against HIV-1 subtype C.


Assuntos
Genoma Viral , HIV-1/genética , África , Sequência de Aminoácidos , Ásia , Células Cultivadas , Clonagem Molecular , HIV-1/classificação , Humanos , Leucócitos Mononucleares/virologia , Macrófagos/virologia , Dados de Sequência Molecular , Filogenia , Receptores CCR5/metabolismo , Alinhamento de Sequência , Transfecção , Replicação Viral
5.
AIDS Res Hum Retroviruses ; 17(5): 423-31, 2001 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-11282011

RESUMO

It is becoming increasingly important to identify and to study human immunodeficiency virus type 1 (HIV-1) circulating recombinant forms (CRFs) with evidence of epidemic spread, since mosaic strains arise frequently, especially in populations where multiple subtypes cocirculate. We describe the almost complete nucleotide sequence of 3 subtype C and D recombinant viruses, selected from a pool of 13 D(gag)-D/C/D(env) perinatally infected infants from Dar es Salaam, Tanzania. All three genomes had cross-over points with approximately the same genomic localization. The subtype C-like sequences were located within pol, vif, vpr, vpu, the first exons of rev and tat, V3, and the U3-R regions of the LTR. Phylogenetic analyses of the full-length genomic sequences from these viruses showed the formation of a distinct subcluster on the HIV-1 subtype D branch. The pattern of recombination of genomes belonging to this new CRF, named CRF10_CD, might have resulted from independent recombination events occurring at high frequency or from a single source that originated earlier in this population. Future surveys will be needed to determine the potential of this CRF for epidemic spread.


Assuntos
Infecções por HIV/virologia , HIV-1/genética , Recombinação Genética/genética , Sequência Consenso , Genoma Viral , Infecções por HIV/congênito , Infecções por HIV/epidemiologia , HIV-1/química , HIV-1/isolamento & purificação , Humanos , Lactente , Filogenia , Tanzânia
6.
J Hum Virol ; 4(1): 16-25, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11213929

RESUMO

OBJECTIVE: To determine whether genotypes from human immunodeficiency virus type 1 (HIV-1) subtypes A, C, or D or intersubtype recombinants have the same probability of being transmitted from mother to child. METHODS: We determined the HIV-1 genetic subtype and maternal risk factors of 51 matched transmitting and nontransmitting mothers from Tanzania. The HIV-1 gag (p24-p7) and env (C2-C5) nucleotide sequences were used for genotype classification, and matched logistic regression analysis was used to assess differences among genotypes. RESULTS: Mothers infected with HIV-1 subtype A (odds ratio, 3.8; 95% CI, 0.8-24.7%), HIV-1 subtype C (odds ratio, 5.1; 95% CI, 1.3-30.8%), or HIV-1 intersubtype recombinant viruses (odds ratio, 5.3; 95% CI, 1.2-33.4%) were more likely to transmit HIV-1 to their infants than mothers infected with HIV-1 subtype D. Lower CD4 cell counts at enrollment were associated with transmission, but CD4 cell counts within each genotype did not explain differences in transmission among HIV-1 genotypes. CONCLUSION: We have shown that HIV-1 genotypes might be associated with differential risk for vertical transmission. These findings provide the first evidence that HIV-1 genetic subtypes may play a role in rates of vertical transmission in an African setting.


Assuntos
Proteínas do Capsídeo , Infecções por HIV/virologia , HIV-1/genética , Proteínas Virais , Sequência de Bases , Capsídeo/genética , Estudos de Casos e Controles , DNA Viral , Método Duplo-Cego , Feminino , Produtos do Gene env/genética , Produtos do Gene gag/genética , Genótipo , Proteína do Núcleo p24 do HIV/genética , Infecções por HIV/sangue , Infecções por HIV/transmissão , HIV-1/classificação , Humanos , Lactente , Recém-Nascido , Dados de Sequência Molecular , Fatores de Risco , Produtos do Gene gag do Vírus da Imunodeficiência Humana
7.
Virology ; 278(2): 390-9, 2000 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-11118362

RESUMO

Human immunodeficiency virus type 1 (HIV-1) subtype C is now responsible for more than half of all HIV-1 infections in the global epidemic and for the high levels of HIV-1 prevalence in southern Africa. To facilitate studies of the biological nature and the underlying molecular determinants of this virus, we constructed eight full-length proviral clones from two asymptomatic and three AIDS patients infected with HIV-1 subtype C from Botswana. Analysis of viral lysates showed that Gag, Pol, and Env structural proteins were present in the virions. In four clones, the analysis suggested inefficient envelope glycoprotein processing. Nucleotide sequence analysis of the eight clones did not reveal frameshifts, deletions, premature truncations, or translational stop codons in any structural, regulatory, or accessory genes. None of the subtype C clones were replication competent in donor peripheral blood mononuclear cells (PBMCs), macrophages, Jurkat(tat) cells, or U87. CD4.CCR5 cells. However, infection by two clones could be rescued by complementation with a functional subtype C envelope clone, resulting in a productive infection of PBMCs, macrophages, and U87. CD4.CCR5 cells.


Assuntos
Produtos do Gene env/genética , HIV-1/classificação , HIV-1/genética , Síndrome da Imunodeficiência Adquirida/virologia , Adulto , Sequência de Aminoácidos , Animais , Botsuana , Células COS , Linhagem Celular , Chlorocebus aethiops , Clonagem Molecular , Sequência Consenso , Feminino , Produtos do Gene env/química , Glioma , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Células Jurkat , Linfócitos/virologia , Macrófagos/virologia , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transfecção , Replicação Viral/genética
8.
J Infect Dis ; 182(5): 1531-5, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11023477

RESUMO

Preliminary preclinical and clinical data suggest that granulocyte-macrophage colony-stimulating factor (GM-CSF) may decrease viral replication. Therefore, 105 individuals with AIDS who were receiving nucleoside analogue therapy were enrolled in a placebo-controlled, double-blind study and were randomized to receive either 125 microgram/m(2) of yeast-derived, GM-CSF (sargramostim) or placebo subcutaneously twice weekly for 6 months. Subjects were evaluated for toxicity and disease progression. A significant decrease in mean virus load (VL) was observed for the GM-CSF treatment group at 6 months (-0.07 log(10) vs. -0.60 log(10); P=.02). More subjects achieved human immunodeficiency virus (HIV)-RNA levels <500 copies/mL at >/=2 evaluations (2% on placebo vs. 11% on GM-CSF; P=.04). Genotypic analysis of 46 subjects demonstrated a lower frequency of zidovudine-resistant mutations among those receiving GM-CSF (80% vs. 50%; P=.04). No difference was observed in the incidence of opportunistic infections (OIs) through 6 months or survival, despite a higher risk for OI among GM-CSF recipients. GM-CSF reduced VL and limited the evolution of zidovudine-resistant genotypes, potentially providing adjunctive therapy in HIV disease.


Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Zidovudina/uso terapêutico , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/virologia , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Método Duplo-Cego , Feminino , Genótipo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue
9.
Virology ; 274(2): 402-11, 2000 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-10964782

RESUMO

A study of the human immunodeficiency virus Type 1 (HIV-1) 5' long terminal repeat (LTR) was performed to determine the extent of variation found within the LTR from 19 mother-infant pairs in Tanzania and to assess whether the LTR is useful in distinguishing maternal sequences that were transmitted to infants. HIV-1 subtypes A, C, and D as well as intersubtype recombinant LTR sequences were detected in mothers and infants. The LTR subtype was 100% concordant between mothers and their infants. Diversity calculations showed a significant reduction in LTR variation in infants compared to their mothers. However, the overall magnitude of LTR variation was less than that found in the env gene from the same individuals. These data suggest a selective constraint active upon the 5' long terminal repeat that is distinct from immune selective pressure(s) directed against HIV-1 structural genes. Detection of maternal LTR variants that were transmitted to infants may yield important information concerning nonstructural determinants of HIV-1 transmission from mother to infant.


Assuntos
Variação Genética/genética , Infecções por HIV/transmissão , Repetição Terminal Longa de HIV/genética , HIV-1/genética , Transmissão Vertical de Doenças Infecciosas , Adulto , Criança , Feminino , Produtos do Gene env/genética , Infecções por HIV/classificação , Infecções por HIV/epidemiologia , HIV-1/classificação , Humanos , Lactente , Mães , Mutação/genética , Filogenia , Seleção Genética , Tanzânia/epidemiologia
10.
J Acquir Immune Defic Syndr ; 23(3): 246-54, 2000 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-10839660

RESUMO

BACKGROUND: Observational studies suggest that poor nutritional status among HIV-infected pregnant women is associated with a higher risk of vertical transmission of HIV. METHODS: We randomized 1083 pregnant women infected with HIV-1 in a double-blind, placebo-controlled trial to examine the effects of supplements of vitamin A and/or multivitamins (excluding vitamin A) using a 2-x-2 factorial design. We report the effects of the supplements on HIV infection defined using polymerase chain reaction (PCR), or death up to 6 weeks postpartum. RESULTS: Of babies in the multivitamin arm 38, (10.1%) were HIV-positive at birth compared with 24 (6.6%) in the no-multivitamin arm (relative risk [RR] = 1.54; 95% CI, 0.94-2.51; p = .08). Of babies born to mothers in the vitamin A arm, 38 (10.0%) were HIV-positive at birth compared with 24 (6.7%) in the no-vitamin A arm (RR, 1.49; 95% CI, 0.91-2.43; p = 0.11). Neither multivitamins nor vitamin A had an effect on HIV status at 6 weeks among those who were HIV-negative at birth (RR = 1.04; 95% CI, 0.65-1.66; p = 0.88) and (RR = 1.30; 95% CI, 0.80-2.09; p = .29, respectively). Similarly, neither supplement was associated with being either HIV-infected or dead at birth (RR, 0.98; 95% CI, 0.76-1.27; p = .89 and RR, 1.01; 95% CI, 0.78-1.31; p = .95, respectively. A beneficial effect of multivitamins on birth weight was limited to babies who were HIV-negative at birth; babies in the multivitamin arm weighed +94 g more compared with those in the no-multivitamin arm (p = .02). Among babies who were HIV-positive at birth, the corresponding difference was -31 g (p = .82). CONCLUSIONS: Vitamin A and multivitamins did not affect the risk of vertical transmission of HIV in utero nor during the intrapartum and early breastfeeding periods. Multivitamins resulted in a significant improvement in birth weight of babies who were HIV-negative at birth but had no effect among those who were HIV-positive. The effect of vitamin supplements on HIV transmission through breastfeeding and on clinical progression of HIV disease is yet to be ascertained.


Assuntos
Suplementos Nutricionais , Infecções por HIV/transmissão , HIV-1 , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Vitaminas/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Morte Fetal/epidemiologia , Morte Fetal/prevenção & controle , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Estado Nutricional , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Fatores de Risco , Tanzânia/epidemiologia , Vitamina A/administração & dosagem , Vitamina A/uso terapêutico , Vitaminas/administração & dosagem
11.
AIDS ; 13(13): 1613-21, 1999 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-10509561

RESUMO

OBJECTIVE: To determine whether the envelope V3 region from HIV-1 subtypes A, C or D had the same probability of being present in intersubtype recombinant genomes. MATERIALS AND METHODS: The envelope C2-C5 and the gag p24-p7 regions from one hundred infants infected perinatally in Tanzania were compared using phylogenetic and recombination analysis. Exact binomial and Fisher's exact tests were used to assess if various genomic regions were more likely to be overrepresented in intersubtype recombinants. RESULTS: Of one hundred HIV-1 positive infants analyzed, twenty-two (22%) showed exclusively subtype A sequence in gag and env. Subtype C accounted for twenty-two infants (22%) whereas nineteen infants (19%) were infected by HIV-1 subtype D. Intersubtype recombinant genomes accounted for thirty-seven infections (37%). The V3 region from subtype A was found in all fifteen A-D recombinants (P = 0.00003) and the V3 region from subtype C was found in all twelve C-D recombinants (P = 0.0002). Conversely, subtype D gag sequences were preferentially represented in the gag of A-D recombinants (P = 0.0003) as well as C-D recombinants (P = 0.002). In A-D recombinants, the V3 region of subtype A was generally surrounded by subtype A C3-C5 sequences. In contrast, the V3 region from subtype C was surrounded by subtype D C3-C5 sequences in C-D recombinants. Significant differences were not found in the number of subtype A or subtype C sequences in A-C recombinants. CONCLUSION: We have shown that several recombinant HIV-1 viruses have been generated and efficiently transmitted to infants in Tanzania. The recombination patterns showed that the V3 region of subtypes A or C was always selected in A-D and C-D recombinants. This selection suggests that the fitness of subtype D-V3 in perinatal transmission may be reduced with respect to V3 from subtype A and/or subtype C. The elevated number of recombinants transmitted perinatally suggests that co-infection or super-infection by two HIV-1 subtypes is not uncommon in this population.


Assuntos
Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/virologia , HIV-1/genética , Fragmentos de Peptídeos/genética , Recombinação Genética , Sequência de Aminoácidos , Genoma , Proteína do Núcleo p24 do HIV/genética , Infecções por HIV/transmissão , HIV-1/classificação , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Dados de Sequência Molecular , Análise de Sequência de DNA , Tanzânia
13.
J Virol ; 73(5): 4427-32, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10196340

RESUMO

To better understand the virological aspect of the expanding AIDS epidemic in southern Africa, a set of 23 near-full-length clones of human immunodeficiency virus type 1 (HIV-1) representing eight AIDS patients from Botswana were sequenced and analyzed phylogenetically. All study viruses from Botswana belonged to HIV-1 subtype C. The interpatient diversity of the clones from Botswana was higher than among full-length isolates of subtype B or among a set of full-length HIV-1 genomes of subtype C from India (mean value of 9. 1% versus 6.5 and 4.3%, respectively; P < 0.0001 for both comparisons). Similar results were observed in all genes across the entire viral genome. We suggest that the high level of HIV-1 diversity might be a typical feature of the subtype C epidemic in southern Africa. The reason or reasons for this diversity are unclear, but may include an altered replication efficiency of HIV-1 subtype C and/or the multiple introduction of different subtype C viruses.


Assuntos
Infecções por HIV/virologia , HIV-1/genética , Sequência de Bases , Botsuana/epidemiologia , Clonagem Molecular , DNA Viral , Infecções por HIV/epidemiologia , HIV-1/classificação , Humanos , Dados de Sequência Molecular , Filogenia
14.
Virology ; 254(2): 220-5, 1999 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-9986788

RESUMO

Retroviruses such as human immunodeficiency virus type 1 (HIV-1) contain two RNA strands per virion, and recombination can occur frequently during reverse transcription. Recombination may occur between HIV-1 genomes of the same subtype or among genomes of two or more distinct subtypes present in an individual. In the current study, we found that recombinatorial events were not limited to viral structural genes such as gag and env, but rather, recombination could likewise occur within the 5' long terminal repeat (LTR). Intersubtype recombinant LTRs among HIV-1 subtypes A, C, and D were found in Tanzanian infants. By introducing novel LTR sequences, these recombinant LTR viruses may further increase the adaptive potential and fitness of HIV-1.


Assuntos
Infecções por HIV/genética , Repetição Terminal Longa de HIV/genética , HIV-1 , Recombinação Genética , Sequência de Bases , Sequência Consenso , Feminino , Produtos do Gene env/genética , Produtos do Gene gag/genética , Variação Genética , Infecções por HIV/transmissão , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Dados de Sequência Molecular , Gravidez , Complicações Infecciosas na Gravidez/virologia , Alinhamento de Sequência , Tanzânia
16.
J Acquir Immune Defic Syndr Hum Retrovirol ; 13(4): 299-307, 1996 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-8948366

RESUMO

HIV-1 isolates are classified phylogenetically in several subtypes or clades according to env and gag coding sequences. Viral subtypes tend to cluster geographically. DNA sequences encoding the p51 subunit of reverse transcriptase were obtained by nested polymerase chain reaction from peripheral blood mononuclear cells of two HIV-1-seropositive individuals from New Delhi and three from Pune, in northern and western India, respectively. These isolates were previously characterized as subtype C according to their env sequences. Based on phylogenetic analysis, the reverse transcriptase coding region of these isolates is distinct from those of subtype A, subtype B, subtype D, and group O of HIV-1 viruses. The nucleotide divergence of these Indian pol sequences (3.3%) is similar to that of existing sequences for subtype B and subtype D viruses. This result supports the epidemiologic data of a more recently introduced HIV-1 epidemic in India. Based on the corresponding env sequences, the pol sequences described in this report are subtype C.


Assuntos
Genes pol/genética , Soropositividade para HIV/genética , HIV-1/genética , Sequência de Aminoácidos , Sequência de Bases , Primers do DNA , DNA Viral/análise , Transcriptase Reversa do HIV/genética , Soropositividade para HIV/epidemiologia , Soropositividade para HIV/virologia , HIV-1/classificação , HIV-1/isolamento & purificação , Humanos , Índia/epidemiologia , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase
18.
Neurology ; 46(6): 1556-60, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8649548

RESUMO

Several case reports have suggested an association between human T-cell lymphotropic virus type II (HTLV-II) infection and chronic neurologic disease. We performed serial neurologic examinations in injection-drug users (IDU), a group known to be at increased risk for HTLV-II infection. At baseline, those infected with HTLV-II alone, human immunodeficiency virus (HIV) alone, or both were significantly more likely to have neurologic disability than uninfected subjects. Longitudinally, HTLV-II infection was independently associated with the development of global neurologic disability and neuropathy, suggesting that HTLV-II causes neurologic disease.


Assuntos
Infecções por HTLV-II/complicações , Doenças do Sistema Nervoso/etiologia , Abuso de Substâncias por Via Intravenosa/complicações , Complexo AIDS Demência/complicações , Complexo AIDS Demência/epidemiologia , Adulto , Alcoolismo/complicações , Alcoolismo/epidemiologia , Doenças dos Gânglios da Base/epidemiologia , Doenças dos Gânglios da Base/etiologia , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/etiologia , Comorbidade , Feminino , Seguimentos , Infecções por HTLV-II/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Modelos de Riscos Proporcionais , Risco , Transtornos de Sensação/epidemiologia , Transtornos de Sensação/etiologia , Índice de Gravidade de Doença , Abuso de Substâncias por Via Intravenosa/epidemiologia , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia
19.
Science ; 271(5253): 1291-3, 1996 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-8638113

RESUMO

Heterosexual transmission by vaginal intercourse accounts for most transmission of human immunodeficiency virus-type 1 (HIV-1) in Africa and Asia but is less important in the HIV-1 epidemics of the United States and Western Europe. Epithelial Langerhans' cells (LCs) represent a possible source of initial cell contact for vaginal infection. Fifteen primary isolates of HIV-1 from U.S. homosexuals and 18 HIV-1 isolates from Thailand heterosexuals were evaluated for growth in LCs of U.S. origin. All the viruses from the Thai heterosexuals, which were subtype E, grew more efficiently in the LCs than any of the viruses from the U.S. homosexuals, which are subtype B. These results suggest that LC tropism is associated with the efficiency of heterosexual transmission of HIV.


Assuntos
Infecções por HIV/transmissão , HIV-1/crescimento & desenvolvimento , Células de Langerhans/virologia , Comportamento Sexual , Doenças Virais Sexualmente Transmissíveis/transmissão , Linhagem Celular , Células Cultivadas , Proteína do Núcleo p24 do HIV/análise , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/isolamento & purificação , Homossexualidade Masculina , Humanos , Macrófagos/virologia , Masculino , Monócitos/virologia , Doenças Virais Sexualmente Transmissíveis/virologia , Linfócitos T/virologia , Tailândia , Estados Unidos , Replicação Viral
20.
Artigo em Inglês | MEDLINE | ID: mdl-8797717

RESUMO

The approach taken in our laboratory to determine viral markers associated with human T cell leukemia virus type I (HTLV-I) disease induction was to compare viral genomes and host immune responses from HTLV-I-infected patients from two geographical areas with significant differences in the incidence rate of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM), Tumaco, Colombia, and Kyushu Island, Japan. These studies showed that TSP/HAM patients have higher antibody levels against viral antigens and a higher proviral load compared to asymptomatic carriers and adult T cell leukemia (ATL) patients. A mutation in the tax gene was found to be associated with TSP/HAM, which in turn correlates with a higher transactivation activity of Tax. In addition, we found that HTLV-I-infected individuals contain infected cells that are clonally expanded. The genomic structure of these expanded clones shows that defective proviruses are present in asymptomatic carriers. A predilection in the defectiveness, however, was found to correlate with the presence (Cosmopolitan molecular genotype) or absence of the tax mutation (Japanese molecular genotype). Our results suggest that defective proviruses retaining structural genes might be a risk factor for TSP/HAM development. Contrary, defective proviruses retaining regulatory genes in the pX region could be a risk factor for ATL development. The molecular mechanism by which these defective proviruses is generated and expressed should give new insight into HTLV-I pathogenesis.


Assuntos
Genoma Viral , Infecções por HTLV-I/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Células Clonais/virologia , Vírus Defeituosos/genética , Anticorpos Antideltaretrovirus/análise , Progressão da Doença , Produtos do Gene tax/genética , Genótipo , Humanos , Leucemia-Linfoma de Células T do Adulto/virologia , Mutação , Paraparesia Espástica Tropical/imunologia , Paraparesia Espástica Tropical/virologia , Reação em Cadeia da Polimerase , Provírus/genética , Tropismo
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