Biomedical subjects

N A Kootstra

Publications and source records attributed to N A Kootstra.

At least 19 recordsLinked to original sources

PubMed2000

Diminished human immunodeficiency virus type 1 reverse transcription and nuclear transport in primary macrophages arrested in early G(1) phase of the cell cycle.

Previously, we and others have demonstrated that the process of reverse transcription of human immunodeficiency virus type 1 (HIV-1) is disturbed in nondividing macrophages and quiescent T lymphocytes. Here we analyzed which phase of the cell cycle in macrophages is crucial for early steps in the HIV-1 replication cycle. HIV-1 Ba-L-inoculated macrophages arrested early in the G(1) phase by n-butyrate contained incomplete products of reverse transcription. In gamma-irradiated macrophages, reverse transcription was successfully completed but proviral integration could not be detected. In these cells, nuclear import was disturbed as reflected by the absence of two-long-terminal-repeat circles. In macrophages arrested late in G(1) phase by aphidicolin or 5, 6-dichloro-1-beta-D-ribofuranosyl-benzimidazole (DRB), reverse transcription was unaffected. Proviral integration occurred efficiently in DRB-treated macrophages, whereas integrated proviral DNA could not be detected after aphidicolin treatment. Arrest at G(2) phase of the cell cycle by nocodazole did not affect reverse transcription or proviral integration. Treatment of macrophages with hydroxyurea (HU), which reduces the intracellular deoxynucleoside triphosphate (dNTP) pool by blocking the de novo synthesis of dNTP, resulted in a dose-dependent inhibition of HIV-1 reverse transcription. This could partially be restored by the addition of nucleoside precursors. Addition of nucleoside precursors enhanced both reverse transcription and cell proliferation. However, the disturbed reverse transcription observed in the nonproliferating and n-butyrate-treated macrophages could not be restored by addition of nucleoside precursors. Similar to observations in quiescent T lymphocytes, incomplete proviral DNA species were arrested in the cytoplasm of the macrophages. Our results indicate that also in primary macrophages the intracellular nucleotide pools and other cellular factors that coincide with late G(1) phase of the cell cycle may contribute to efficient reverse transcription and nuclear localization.

Biological Transport↗

PubMed1999

Phenotype of HIV-1 lacking a functional nuclear localization signal in matrix protein of gag and Vpr is comparable to wild-type HIV-1 in primary macrophages.

Human immunodeficiency virus type 1 (HIV-1) is considered to infect nondividing cells because nuclear localization signals (NLS) in matrix (MA, p17(Gag)) and Vpr allow active nuclear transport of the preintegration complex. Previous studies demonstrated that HIV-1 reverse transcription is successful only in cells with proliferative potential, thus restricting HIV-1 replication to cycling cells. To sort out this apparent discrepancy we compared the phenotype of a chimeric HIV-1 variant lacking a functional Vpr and MA-NLS (R7. deltaVpr.deltaNLS), and previously described to lack replicative capacity in macrophages and growth-arrested cells, with a chimera lacking a functional Vpr (R7.deltaVpr). Both variants replicated efficiently in primary macrophages, with only minimal differences in the kinetics of reverse transcription, integration, or p24 production. In agreement with our previous observation, elongation of reverse transcription was restricted to the proliferating subpopulation of macrophages. Replication of R7.deltaVpr and R7.deltaVpr.deltaNLS could also be demonstrated in aphidicolin-treated macrophages, indicating efficient nuclear transport in G1/S phase-arrested cells. In conclusion, our results confirm the dependency of the process of HIV-1 reverse transcriptase on cell proliferation in primary macrophages and exclude an important role of MA-NLS and Vpr in macrophage infection.

Bromodeoxyuridine↗

PubMed1999

R5 strains of human immunodeficiency virus type 1 from rapid progressors lacking X4 strains do not possess X4-type pathogenicity in human thymus.

Some individuals infected with only R5 strains of human immunodeficiency virus type 1 progress to AIDS as quickly as individuals harboring X4 strains. We determined that three R5 viruses were much less pathogenic than an X4 virus in SCID-hu Thy/Liv mice, suggesting that R5 virus-mediated rapid disease progression is associated with host, not viral, factors.

Animals↗

PubMed1998

Proliferation-dependent replication in primary macrophages of macrophage-tropic HIV type 1 variants.

We previously demonstrated that completion of reverse transcription in macrophages inoculated with the HIV-1 Ba-L variant was established only in the subpopulation of cells with proliferative capacity. In our present study we further extended this observation with three additional HIV-1 isolates, being the macrophage-tropic ADA strain and two primary macrophage-tropic HIV-1 variants isolated from cerebrospinal fluid and from bronchoalveolar lavage from AIDS patients. On inoculation, irrespective of the virus variant used, elongated reverse transcription products could be demonstrated only in macrophages that had proliferated during inoculation as evidenced by the incorporation of bromodeoxyuridine (BrdU), a thymidine analog. The presence of newly synthesized early products of reverse transcription also in the BrdU-negative fraction indicated that viral entry is not disturbed in nondividing cells. Our data indicate that the process of reverse transcription is dependent on cellular conditions that coincide with cell proliferation, and therefore that HIV-1 replication is restricted to cells with proliferative potential.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Infectious cellular load in human immunodeficiency virus type 1 (HIV-1)-infected individuals and susceptibility of peripheral blood mononuclear cells from their exposed partners to non-syncytium-inducing HIV-1 as major determinants for HIV-1 transmission in homosexual couples.

To study risk factors for homosexual transmission of human immunodeficiency virus type 1 (HIV-1), we compared 10 monogamous homosexual couples between whom transmission of HIV-1 had occurred with 10 monogamous homosexual couples between whom HIV-1 transmission had not occurred despite high-risk sexual behavior. In the group of individuals who did not transmit virus, peripheral cellular infectious load was lower and the CD4+ T-cell counts were higher than in the group of transmitters. HIV-1 RNA levels in serum did not differ between transmitters and nontransmitters. Compared with peripheral blood mononuclear cells (PBMC) from normal healthy blood donors, 8 of 10 nonrecipients and only 3 of 8 recipients had PBMC with reduced susceptibility to in vitro infection with non-syncytium-inducing (NSI) HIV-1 variants isolated from either their respective partners or an unrelated individual. No difference in susceptibility was observed for infection with a syncytium-inducing variant. Among the individuals who had PBMC with reduced susceptibility, five nonrecipients and one recipient had PBMC that were equally or even less susceptible to NSI variants than PBMC that had low susceptibility and that were derived from healthy blood donors that were heterozygous for a 32-bp deletion in the CCR5 gene (CCR5 delta32). Three of these individuals (all nonrecipients) had a CCR5 delta32 heterozygous genotype themselves, confirming an association between low susceptibility to NSI variants and CCR5 delta32 heterozygosity. All three recipients with less susceptible PBMC had partners with a high infectious cellular load; inversely, both nonrecipients with normally susceptible PBMC had partners with a very low infectious cellular load. These results suggest that a combination of susceptibility of target cells and inoculum size upon homosexual exposure largely determines whether HIV-1 infection is established.

Adult↗

PubMed1998

Analysis of the temporal relationship between human immunodeficiency virus type 1 quasispecies in sequential blood samples and various organs obtained at autopsy.

We studied the temporal relationship between human immunodeficiency type 1 (HIV-1) quasispecies in tissues and in peripheral blood mononuclear cells (PBMC) of infected individuals. Sequential PBMC and tissue samples from various organs obtained at autopsy from three patients who died of AIDS-related complications were available for analysis. Biological HIV-1 clones were isolated from PBMC samples, and cellular tropism and syncytium-inducing (SI) capacity were determined. Genomic DNA was isolated from 1 cm3 of organ tissue, and proviral DNA was amplified by means of PCR and cloned with the PGEM-T vector system. A 185-bp region encompassing the third variable domain of the virus envelope, known to influence HIV-1 biological properties, was sequenced. HIV-1 could be amplified from all PBMC and organ samples, except from liver tissue for two patients. Both SI and non-syncytium-inducing (NSI) genotypes could be detected in the different tissues. Tissue-specific quasispecies were observed in brain, lung, and testis. Lymphoid tissues, such as bone marrow, lymph node, and spleen, harbored several different variants similar to those detected in blood in the last PBMC samples. In general, only tissues in which macrophages are likely to be the main target cell for HIV-1 harbored NSI HIV-1 sequences that clustered separately. Both SI and NSI sequences that clustered with sequences from late-stage PBMC were present in other tissues, which may indicate that the presence of HIV-1 in those tissues is secondary to lymphocyte infiltration rather than to tissue tropism of HIV-1 itself. These data suggest that the viral reservoir may be limited, which will have important implications for the success of HIV-1 eradication.

Amino Acid Sequence↗

PubMed1997

Analysis of CD8+ T lymphocyte-mediated nonlytic suppression of autologous and heterologous primary human immunodeficiency virus type 1 isolates.

Nonlytic CD8+ T lymphocyte antiviral factor (CAF) activity has been described as having an important role in the clinical course of human immunodeficiency virus type 1 (HIV-1) infection. Testing of CAF activity against autologous viruses isolated at approximately the same time points showed that CD8+ T lymphocytes from long-term survivors indeed possessed high CAF activity. However, in four of six progressors to AIDS, we observed the same amount of CAF activity in the face of increasing cellular HIV-1 load. In the other two progressors, CAF activity seemed preserved over time whereas the susceptibility of the virus isolate obtained late in infection seemed to be diminished. In a heterologous system, CAF activity of CD8+ T lymphocytes from 13 HIV-1-positive individuals did not correlate with CD4+ T lymphocyte counts. In two of three patients, syncytium-inducing (SI) HIV-1 variants, which are associated with a progressive clinical course, appeared to have a somewhat reduced susceptibility to CAF activity as compared to their coexisting non-SI HIV-1 variants. In a large donor group, suppression of SI isolates (as compared to non-SI isolates) mediated by heterologous CD8+ T lymphocytes was reduced. CD8+ T lymphocytes from five of six HIV-1-positive individuals suppressed HIV-1 replication in macrophages. CD8+ T lymphocytes from noninfected donors, even from cord blood, already had high CAF activity, suggesting that induction of this activity is neither virus nor HIV-1 specific.

Anti-HIV Agents↗

PubMed1996

Relation between changes in cellular load, evolution of viral phenotype, and the clonal composition of virus populations in the course of human immunodeficiency virus type 1 infection.

The relationship between the evolution of human immunodeficiency virus type 1 (HIV-1) biologic phenotype, changes in the proportion of infected peripheral blood mononuclear cells, and the relative contribution of non-syncytium-inducing (NSI) and syncytium-inducing (SI) HIV-1 variants to virus load was studied during the course of HIV-1 infection. In 65 HIV-1-infected subjects, the proportion of infected CD4 T cells was higher in persons who carried SI variants. Longitudinal studies revealed that the emergence of SI HIV-1 variants can occur at relatively low numbers of HIV-1-infected cells. Emergence of SI variants frequently coincided with an increase of virus load due to an expansion of both NSI and SI variants, although the contribution of SI viruses to the total virus population significantly increased with time after SI phenotype conversion. These data indicate that NSI to SI phenotype conversion, rather than resulting from high virus load, is part of the sequence of events that leads to increased virus load and CD4 cell depletion.

CD4 Lymphocyte Count↗

PubMed1996

Changes in cellular virus load and zidovudine resistance of syncytium-inducing and non-syncytium-inducing human immunodeficiency virus populations under zidovudine pressure: a clonal analysis.

Zidovudine treatment preferentially benefits persons with only non-syncytium-inducing (NSI) human immunodeficiency virus type 1 (HIV-1) variants. To understand this differential efficacy, changes in cellular virus load, clonal composition of HIV-1 populations, and development of resistance-conferring reverse transcriptase mutations were studied in 17 persons initiating zidovudine therapy. Zidovudine treatment resulted in larger and more sustained decreases in cellular virus load in persons with NSI variants only compared with persons also carrying syncytium-inducing (SI) variants. Although the former group had a delayed emergence of resistance mutations, differences in initial responses between the 2 groups were independent of the emergence of resistance mutations. Changes in virus load in subjects also carrying SI variants were due mainly to loss of coexisting NSI virus. Resistance mutations emerged at similar rates in both coexisting variants. Data suggest that mechanisms other than drug resistance are necessary to completely explain the phenotype-dependent benefit of zidovudine.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Productive HIV-1 infection of macrophages restricted to the cell fraction with proliferative capacity.

Retroviruses establish productive infection only in proliferating cells. Macrophages are often considered to be non-proliferating in vitro yet are susceptible to HIV-1 infection. This has led to the conclusion that HIV-1 can establish infection independent of host cell proliferation. We here report that a small proportion of macrophages does have proliferative capacity. A comparable small fraction of monocyte derived macrophages (MDM) supported productive HIV-1 infection as demonstrated in limiting dilution culture. Fluorescence activated cell sorting on the basis of incorporation of BrdUrd, a thymidine analog, and subsequent PCR analysis revealed the presence of proviral DNA only in the BrdUrd positive cell fraction with DNA synthesizing activity. To identify which phase of cell cycle is required for establishment of productive infection, growth arrest in G1 or G1/S phase prior to inoculation was performed. gamma-Irradiation, which arrests primary cells in G1, prevented both cell proliferation and establishment of productive infection in MDM. Treatment of MDM with aphidicolin, a specific inhibitor of DNA polymerase alpha and delta which arrests cells in G1/S phase of the cell cycle, also inhibited DNA synthesis but did not prevent establishment of productive infection which is completely analogous to observations in T cells. Our data thus indicate that not cell division itself but cellular conditions that coincide with cell proliferation are apparently indispensable for establishment of productive infection.

Aphidicolin↗

PubMed1994

Viro-immunological studies in acute HIV-1 infection.

OBJECTIVE: To monitor a patient who presented with symptomatic HIV-1 infection for virological and immunological parameters in relation to the clinical course. METHODS: Virological studies included determination of frequency of productively HIV-1-infected peripheral blood mononuclear cells (PBMC) and viral RNA load in plasma and p24 antigenaemia. Immunological studies included the analysis of T-cell subsets, the expression of activation markers, CD45RO and CD45RA antigens, the frequency of cells programmed for death, and T-cell function. RESULTS: During the first week post onset of primary HIV-1 infection symptoms high plasma titres of p24 and HIV-1 RNA were observed. The number of productively HIV-1-infected PBMC peaked, coinciding with CD4+ T lymphocytopaenia, during week 2 when clinical improvement started. CD8+ T lymphocytosis was observed 10 days post onset of clinical symptoms, the expanded cell population being of the CD8+CD38+, CD8+CD27+ and CD8+CD28- phenotype. CD8+ T lymphocytosis was paralleled by a high percentage of cells undergoing programmed cell death on in vitro culture. In vitro T-cell function was severely depressed during the first 10 days post onset of clinical symptoms. Within about 3 weeks, following resolution of clinical symptoms, phytohaemagglutinin-induced proliferation was restored to normal levels while responses to the CD3 monoclonal antibody only showed a partial restoration. During follow-up, concomitant with the rise of activated CD8+ T cells, p24 antigen levels and viral RNA load in serum as well as the number of HIV-producing PBMC steeply declined after 2 weeks. CONCLUSION: These findings demonstrate HIV-1-induced abnormalities during severe clinical symptoms of primary HIV-1 infection. The subsequent strong immune response, which is believed to be responsible for efficient control of viral replication, appears to precede clinical improvement.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Interference of interleukin-10 with human immunodeficiency virus type 1 replication in primary monocyte-derived macrophages.

Previously we demonstrated an inhibitory effect of interleukin-4 (IL-4) on establishment of human immunodeficiency virus type 1 (HIV-1) infection in primary macrophages. The reported similarities between the biological effects of IL-4 and IL-10 prompted us to study the effect of IL-10 on HIV-1 replication. Treatment of primary macrophages with IL-10 resulted in inhibition of HIV-1 infection. This inhibitory effect was specific for macrophages, since IL-10 did not interfere with HIV-1 replication in primary T cells. Semiquantitative PCR analysis excluded an inhibitory effect of IL-10 on virus entry and reverse transcription. Effects of IL-10 on HIV-1 long terminal repeat-driven chloramphenicol acetyltransferase activity also could not be demonstrated in a transient expression system in primary derived macrophages. In agreement with this, Northern (RNA) blot analysis demonstrated equal amounts of viral RNA species irrespective of IL-10 treatment, also excluding an inhibitory effect on elongation of virus transcription. Monocyte-derived macrophages (MDM) treated with IL-10 after HIV-1 inoculation showed accumulation of apparently mature p24 protein suggestive of an inhibitory effect at the level of virus assembly. IL-10 treatment of MDM prior to HIV-1 inoculation did not result in accumulation of p24 protein. Immunoblot analysis indeed showed the absence of mature p24 and gp120 but accumulation of the Pr53 gag-encoded protein in HIV-1-inoculated, IL-10-pretreated MDM, suggesting an inhibitory effect at the level of protein processing. A combination of IL-4 and IL-10 resulted in a cumulative inhibitory effect on HIV-1 replication in MDM. The recent observation that in the course of HIV-1 infection a shift occurs in the production of IL-2/gamma interferon toward enhanced IL-4 and IL-10 production and the reported shift from preferential macrophage-tropic towards preferential T-cell-tropic HIV-1 variants with progression of disease suggest that cytokines have an important role in the in vivo regulation of HIV-1 tropism.

Base Sequence↗

PubMed1994

HIV-1 macrophage tropism is determined at multiple levels of the viral replication cycle.

The ability of HIV-1 to infect macrophages is thought to be essential in AIDS pathogenesis. We tested the ability of 19 primary virus isolates to infect monocyte-derived macrophages (MDM) from different donors. Two HIV-1 isolates were able to establish a productive infection in MDM from all donors tested, whereas eight completely lacked this capacity. Next to these isolates with extreme phenotypes, 50% of the primary isolates under study displayed an intermediate phenotype. These intermediate macrophage-tropic isolates established a productive infection in MDM from some but not all donors tested. PCR analysis demonstrated that the capacity to replicate in MDM could be determined at the previously described level of virus entry. However, for intermediate macrophage-tropic isolates replication was abrogated at the level of reverse transcription. Entry of highly macrophage-tropic isolates resulted in efficient completion of the reverse transcription process, whereas entry of intermediate macrophage-tropic isolates did not. Our experiments indicate that primary HIV-1 isolates may differ in their dependency on cellular factors required for reverse transcription in MDM. Differences in susceptibility of MDM for in vitro HIV-1 infection suggest variation in the availability of these cellular factors between MDM from different individuals.

Adult↗

PubMed1994

Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission.

Macrophage-tropic, non-syncytium-inducing, HIV-1 variants predominate in the asymptomatic phase of infection and may be responsible for establishing infection in an individual exposed to the mixture of HIV-1 variants. Here, genotypical and phenotypical characteristics of virus populations, present in sexual, parenteral, or vertical donor-recipient pairs, were studied. Sequence analysis of the V3 domain confirmed the presence of a homogeneous virus population in recently infected individuals. Biological HIV-1 clones were further characterized for syncytium inducing capacity on the MT2 cell line and for macrophage tropism as defined by the appearance of proviral DNA upon inoculation of monocyte-derived macrophages. Both sexual and parenteral transmission cases revealed a selective outgrowth in the recipient of the most macrophage-tropic variant(s) present in the donor. In three out of five vertical transmission cases, more than one highly macrophage-tropic virus variant was present in the child shortly after birth, suggestive of transmission of multiple variants. In three primary infection cases, homogeneous virus populations of macrophage-tropic, non-syncytium-inducing variants were present prior to seroconversion, thus excluding humoral immunity as the selective pressure in favour of macrophage-tropic variants. These observations may have important implications for vaccine development.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Early replication steps but not cell type-specific signalling of the viral long terminal repeat determine HIV-1 monocytotropism.

The expression of human immunodeficiency virus type 1 (HIV-1) is enhanced after cell activation because of the interaction of cell-encoded nuclear factors that interact with binding sites in the long terminal repeats (LTRs). Here we studied the contribution of cell type-specific activation signals to differences in cytotropism of HIV-1 variants. Four closely related molecular HIV-1 clones with distinct biological phenotypes and different capacities to replicate in primary monocyte-derived macrophages (MDMs) or T cell lines were used. Sequence analysis of these LTRs revealed variation in functionally important regions. Adaptation of virus variants to particular host cells by differences in LTR responsiveness was analyzed. LTR-CAT constructs were transiently transfected in T cells that were stimulated with T cell-specific activation signals such as combinations of anti-CD3 or anti-CD28 MoAB or in primary monocytes that were stimulated with IL-3, IL-4, or GM-CSF. No differences in responsiveness to cell type-specific signals were demonstrated. To further elucidate the level of restriction in cell tropism, transfection of four full-length infectious molecular HIV-1 clones into 5-day cultured MDMs was performed. From all clones, competent virus could be rescued from MDMs by coculture with PHA-stimulated PBLs. However, following cell-free inoculation, proviral DNA could be detected by PCR analysis only in monocytes exposed to HIV-1 clones that previously were shown to establish productive infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

PubMed1993

Lack of T cell dysfunction and programmed cell death in human immunodeficiency virus type 1-infected chimpanzees correlates with absence of monocytotropic variants.

In asymptomatic human immunodeficiency virus (HIV) infection in humans, disturbed T cell functions such as anergy and programmed cell death, thought to result from inappropriate signaling by antigen-presenting cells due to HIV infection, precede increase in virus load, decline in CD4+ T cell numbers, and subsequent disease progression. Here, in 3 long-term HIV-1-infected asymptomatic chimpanzees, antigen-presenting cell function was intact and T cells had normal proliferative capacity with no evidence of HIV-1-associated programmed cell death. Polymerase chain reaction analysis demonstrated low frequencies of cells harboring proviral DNA. Primary virus isolation from the infected animals demonstrated the absence of monocytotropic HIV-1 variants, in concordance with complete insusceptibility of chimpanzee monocytes for HIV-1 infection. Possibly, because of the incapacity of HIV-1 to infect monocytes, systemic immune dysfunction will not occur, contributing to controlled viral replication and maintenance of the asymptomatic state in HIV-infected chimpanzees.

Amino Acid Sequence↗

PubMed1992

Differential tropism of clinical HIV-1 isolates for primary monocytes and promonocytic cell lines.

Previously we demonstrated a correlation between a nonsyncytium-inducing (NSI), non-T-cell line tropic phenotype of HIV-1 isolates and the capacity to replicate in primary monocyte-derived macrophages (MDM). Here we demonstrate that these NSI, monocytotropic HIV-1 isolates lack the capacity to replicate in two promonocytic cell-lines, HL60 and U937. In contrast, most syncytium-inducing (SI) HIV-1 isolates with tropism for T-cell lines and generally non-monocytotropic were able to establish a productive infection in promonocytic cell lines. Similar differences in tropism for monocytes and promonocytic cell lines were observed with infectious molecular clones. Our results indicate that virological studies on promonocytic cell lines do not necessarily pertain to the HIV-1 infection of monocytes in vivo.

Cell Line↗

PubMed1992

Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population.

The composition of human immunodeficiency virus type 1 (HIV-1) clonal populations at different stages of infection and in different compartments was analyzed. Biological HIV-1 clones were obtained by primary isolation from patient peripheral blood mononuclear cells under limiting dilution conditions, with either blood donor peripheral blood lymphocytes or monocyte-derived macrophages (MDM) as target cells, and the biological phenotype of the clones was analyzed. In asymptomatic individuals, low frequencies of HIV-1 clones were observed. These clones were non-syncytium inducing and preferentially monocytotropic. In individuals progressing to disease, a 100-fold increase in frequencies of productively HIV-1-infected cells was observed as a result of a selective expansion of nonmonocytotropic clones. In a person progressing to AIDS within 19 months after infection, only syncytium-inducing clones were detected, shifting from MDM-tropic to non-MDM-tropic over time. From his virus donor, a patient with wasting syndrome, only syncytium-inducing clones, mostly non-MDM-tropic, were recovered. Parallel clonal analysis of HIV-1 populations in cells present in bronchoalveolar lavage fluid and peripheral blood from an AIDS patient revealed a qualitatively and quantitatively more monocytotropic virus population in the lung compartment than in peripheral blood at the same time point. These findings indicate that monocytotropic HIV-1 clones, probably generated in the tissues, are responsible for the persistence of HIV-1 infection and that progression of HIV-1 infection is associated with a selective increase of T-cell-tropic, nonmonocytotropic HIV-1 variants in peripheral blood.

Acquired Immunodeficiency Syndrome↗