Latent Human Immunodeficiency Virus Infection Research Articles

Dynamic analysis of a latent HIV infection model with CTL immune and antibody responses

This paper develops a mathematical model to investigate the Human Immunodeficiency Virus (HIV) infection dynamics. The model includes two transmission modes (cell-to-cell and cell-free), two adaptive immune responses (cytotoxic T-lymphocyte (CTL) and antibody), a saturated CTL immune response, and latent HIV infection. The existence and local stability of equilibria are fully characterized by four reproduction numbers. Through sensitivity analyses, we assess the partial rank correlation coefficients of these reproduction numbers and identify that the infection rate via cell-to-cell transmission, the number of new viruses produced by each infected cell during its life cycle, the clearance rate of free virions, and immune parameters have the greatest impact on the reproduction numbers. Additionally, we compare the effects of immune stimulation and cell-to-cell spread on the model’s dynamics. The findings highlight the significance of adaptive immune responses in increasing the population of uninfected cells and reducing the numbers of latent cells, infected cells, and viruses. Furthermore, cell-to-cell transmission is identified as a facilitator of HIV transmission. The analytical and numerical results presented in this study contribute to a better understanding of HIV dynamics and can potentially aid in improving HIV management strategies.

Nanodepots Encapsulating a Latency Reversing Agent and Broadly Neutralizing Antibody Enhance Natural Killer Cell Cytotoxicity Against an in vitro Model of Latent HIV.

Current antiretroviral therapies (ART) for human immunodeficiency virus (HIV) are not curative, as the virus persists in latent reservoirs, requiring lifelong adherence to ART and increasing the risk of co-morbidities. "Shock and kill" approaches to reactivate HIV from latent reservoirs followed by administration of anti-HIV drugs represent a promising strategy for eradicating latent HIV. To achieve effective shock and kill, we describe a strategy to eradicate the HIV reservoir that combines latency reversing agents (LRAs), broadly neutralizing antibodies (bnAbs), and natural killer (NK) cells. This strategy utilizes a polymer nanodepot (ND) that co-encapsulates the LRA and bnAb to reactivate latent infection and elicit enhanced cytotoxicity from co-administered NK cells. Poly(lactic-co-glycolic acid) (PLGA) NDs were synthesized using the nanoprecipitation method to co-encapsulate an LRA (TNF-α) and a bnAb (3BNC117) (TNF-α-3BNC117-NDs). ACH-2 cells were used as a cellular model of latent HIV infection. An NK92 subline, genetically modified to constitutively express the Fc receptor CD16, was administered to ACH-2 cells in combination with TNF-α-3BNC117-NDs. ACH-2 cell death and extracellular p24 were measured via flow cytometry and ELISA, respectively. Stable PLGA NDs co-encapsulated TNF-α and 3BNC117 with high efficiencies and released these agents in physiological conditions. NK92 phenotype remained similar in the presence of TNF-α-3BNC117-NDs. TNF-α released from NDs efficiently reactivated HIV in ACH-2 cells, as measured by a 3.0-fold increase in the frequency of intracellular p24 positive cells. Released 3BNC117 neutralized and bound reactivated virus, targeting 57.5% of total ACH-2 cells. Critically, TNF-α-3BNC117-NDs significantly enhanced NK92 cell-mediated killing of ACH-2 cells (1.9-fold) and reduced extracellular levels of p24 to baseline. These findings suggest the therapeutic potential of our novel ND-based tripartite strategy to reactivate HIV from latently infected cells, generate an HIV-specific site for bnAb binding, and enhance the killing of reactivated HIV-infected target cells by NK92 cells.

μ-Lat: A mouse model to evaluate human immunodeficiency virus eradication strategies.

A critical barrier to the development of a human immunodeficiency virus (HIV) cure is the lack of a scalable animal model that enables robust evaluation of eradication approaches prior to testing in humans. We established a humanized mouse model of latent HIV infection by transplanting "J-Lat" cells, Jurkat cells harboring a latent HIV provirus encoding an enhanced green fluorescent protein (GFP) reporter, into irradiated adult NOD.Cg-Prkdcscid Il2rgtm1Wjl /SzJ (NSG) mice. J-Lat cells exhibited successful engraftment in several tissues including spleen, bone barrow, peripheral blood, and lung, in line with the diverse natural tissue tropism of HIV. Administration of tumor necrosis factor (TNF)-α, an established HIV latency reversal agent, significantly induced GFP expression in engrafted cells across tissues, reflecting viral reactivation. These data suggest that our murine latency ("μ-Lat") model enables efficient determination of how effectively viral eradication agents, including latency reversal agents, penetrate, and function in diverse anatomical sites harboring HIV in vivo.

A prospective cohort study of outcomes for isoniazid prevention therapy: a nested study from a national QI collaborative in Uganda

BackgroundTuberculosis (TB) and human immunodeficiency virus (HIV) co-infection constitute a deadly infectious disease synergy disease and major public health problem throughout the world. The risk of developing active TB in people living with HIV (PLHIV) is 21 times higher than the rest of the world population. The overlap of latent TB infection and HIV infection has resulted in marked increases in TB incidence in countries with dual epidemics. Although antiretroviral therapy (ART) is the single most significant way to reduce incident TB in PLHIV, besides early ART initiation, isoniazid preventive therapy (IPT) is the key intervention to prevent TB among PLHIV. This prospective cohort and longitudinal study aimed to document; retention, adherence, development of active TB disease, possible adverse drug reactions and completion among patients initiated on IPT in Jan 2019.MethodsThis was both a prospective cohort and longitudinal study nested within a national quality improvement collaborative in which multiple quality improvement teams tested changes in care delivery to improve the delivery of IPT. The prospective cohort were HIV patients without TB disease initiated on a dosage of Isoniazid 300 mg/day for adults and 150 mg/day for children for a period of 6 months. Association statistics were used to describe patient characteristics and outcomes. Variables with p-value < 0.05 were used to determine linear by linear associations between patient characteristics assumed to influence both primary and secondary outcomes. Variables with a p-value < 0.05 were included in the logistical regression model. The final model included those factors that retained statistical significance. The odds ratios (OR) and adjusted OR (AOR) along with its 95% confidence interval were used to determine the power of relationship in determining the outcomes of interest. The model was tested for fitness using goodness-of-fit Hosmer–Lemeshow tests.ResultsThe completion of IPT was at 89%. A significant proportion of patients adhered to treatment (89%) and kept their appointment schedules-retention (89%). All patients (100%) received IPT at each appointment visit. Only 4% of patients experienced side effects of isoniazid (INH) but none of them developed active TB at the end of the 6 month INH dose. Multivariate logistic regression analysis of covariates of IPT completion revealed a strong and statistical association between IPT completion and age, gender, retention and side effects of INH. Our multivariate model found that children below 15 years were less likely to complete INH than patients ≥ 15 years (AOR = 0.416, p = 0.230, df = 1). Female patients were 2 times more likely to complete INH dose than male patients (AOR = 1.598, p = 0.018). Patients who kept all their appointment schedules were 10 times more likely to complete IPT than those who missed one or more schedules (AOR = 10.726, p = 0.000, df = 1). We also found that patients who did not report any side effects associated with INH were 2 times more likely to complete INH (AOR = 1.958, p = 0.016, df = 1) than patients who reported one or more side effects.ConclusionTreatment completion is the end-point of the IPT initiation strategy in Uganda. With a completion rate of 89%, our results seem re-assuring and suggest that improvement collaborative is an effective approach to achieving results through combined efforts. The high rates of completion are encouraging indicators of progress in the implementation of collaborative activities in the study setting. However, such collaboratives would require periodic evaluation to prevent possible relapses in progress attained.

Antibody-dependent effector functions against HIV decline in subjects receiving antiretroviral therapy.

Combination antiretroviral therapy (cART) effectively controls human immunodeficiency virus (HIV) infection but does not eliminate HIV, and lifelong treatment is therefore required. HIV-specific cytotoxic T lymphocyte (CTL) responses decline following cART initiation. Alterations in other HIV-specific immune responses that may assist in eliminating latent HIV infection, specifically antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP), are unclear. A cohort of 49 cART-naive HIV-infected subjects from Thailand (mean baseline CD4 count, 188 cells/µL; mean viral load, 5.4 log10 copies/mL) was followed for 96 weeks after initiating cART. ADCC and ADP assays were performed using serum samples obtained at baseline and after 96 weeks of cART. A 35% reduction in HIV type 1 envelope (Env)-specific ADCC-mediated killing of target cells (P<.001) was observed after 96 weeks of cART. This was corroborated by a significant reduction in the ability of Env-specific ADCC antibodies to activate natural killer cells (P<.001). Significantly reduced ADP was also observed after 96 weeks of cART (P=.018). This longitudinal study showed that cART resulted in significant reductions of HIV-specific effector antibody responses, including ADCC and ADP. Therapeutic vaccines or other immunomodulatory approaches may be required to improve antibody-mediated control of HIV during cART.

Glycoproteomic analysis identifies human glycoproteins secreted from HIV latently infected T cells and reveals their presence in HIV+ plasma

Glycoproteins secreted into plasma from T cells infected with human immunodeficiency virus (HIV) latent infection may provide insight into understanding the host response to HIV infection in vivo. Glycoproteomics, which evaluates the level of the glycoproteome, remains a novel approach to study this host response to HIV. In order to identify human glycoproteins secreted from T cells with latent HIV infection, the medium from cultured HIV replication-competent T cells was compared with the medium from cultured parental A3.01 cells via solid phase extraction of glycopeptides (SPEG) and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Using these methods, 59 human glycoproteins were identified as having significantly different abundance levels between the media from these two cell lines. The relevance of these 59 proteins to HIV infection in vivo was assessed in plasma from HIV+ and HIV- subjects. Comparison between T cell and plasma revealed that six glycoproteins (galectin-3-binding protein, L-selectin, neogenin, adenosine deaminase CECR1, ICOS ligand and phospholipid transfer protein) were significantly elevated in the HIV+ T cells and plasma studies. These findings suggest that the response of T cells harboring latent HIV infection contributed, in part, to the glycoprotein changes in HIV+ plasma. These proteins, once validated, could provide insight into host-HIV interaction.

Smallpox containment updated: considerations for the 21st century

Smallpox containment updated: considerations for the 21st century

Effects of prostratin on T-cell activation and human immunodeficiency virus latency.

Human immunodeficiency virus (HIV) replication is linked to cellular gene transcription and requires target cell activation. The latent reservoir of HIV-1 in quiescent T cells is thought to be a major obstacle to clearance of infection by highly active antiretroviral therapy (HAART). Thus, identification of agents that can induce expression of latent virus may, in the presence of HAART, allow elimination of the infected cells by the immune response. We previously used the SCID-hu (Thy/Liv) mouse model to establish that activation-inducible HIV can be generated at high frequency during thymopoiesis. Latently infected mature thymocytes can be exported into the periphery, providing an efficient primary cell model to determine cellular activation signals that induce renewed expression of latent virus. Here we characterized the effects of prostratin, a non-tumor-promoting phorbol ester, on primary human peripheral blood lymphocytes (PBLs) and assessed its ability to reactivate latent HIV infection from thymocytes and PBLs in the SCID-hu (Thy/Liv) model. Prostratin stimulation alone did not induce proliferation of quiescent PBLs; however, it could provide a secondary signal in the context of T-cell receptor stimulation or a primary activation signal in the presence of CD28 stimulation to induce T-cell proliferation. While prostratin alone was not sufficient to allow de novo HIV infection, it efficiently reactivated HIV expression from latently infected cells generated in the SCID-hu mouse. Our data indicate that prostratin alone is able to specifically reactivate latent virus in the absence of cellular proliferation, making it an attractive candidate for further study as an adjunctive therapy for the elimination of the latent HIV reservoir.

The Management of Pain

The Management of Pain

Compounds That Target Novel Cellular Components Involved in HIV-1 Transcription

Therapeutic intervention designed to block expression of human immunodeficiency virus (HIV) at a cellular level may slow the clinical progression of HIV-1 disease. Cellular models of latent (OM-10.1 and U1) and chronic (8E5) HIV infection were used to evaluate two benzothiophene derivatives, PD 121871 and PD 144795, for an ability to inhibit HIV activation and expression. The benzothiophene derivatives were effective at micromolar concentrations in preventing tumor necrosis factor alpha (TNF alpha)-induced HIV-1 expression in OM 10.1 and U1 cultures. These compounds inhibited the activation of HIV-1 transcription; however, this inhibition was selective in that another TNF alpha-induced response, the transcription of autocrine TNF alpha, was unaffected. Constitutive HIV-1 expression by chronically infected 8E5 cells was also significantly reduced when treated with these experimental compounds. In TNF alpha-treated OM-10.1 cultures, the inhibition of HIV-1 transcription by these compounds was not due to a block of nuclear factor-kappa B induction. The benzothiophene derivatives also inhibited HIV-1 activation by phorbol ester treatment of OM-10.1 promyelocytes, although no inhibition of cellular differentiation toward a macrophage-like phenotype was observed. Furthermore, these experimental compounds induced a state of HIV-1 latency in cytokine-activated OM-10.1 cultures even when maintained under constant TNF alpha stimulation. The benzothiophene derivatives did not inhibit the activity of the HIV-1 trans-activator, Tat, when evaluated in transient transfection assays. The benzothiophene derivatives appear to inhibit a critical cellular component, distinct from nuclear factor-kappa B, involved in HIV transcription and may serve to identify new therapeutic targets to restrict HIV expression.

Analysis of human immunodeficiency virus-infected tissues by amplification and in situ hybridization reveals latent and permissive infections at single-cell resolution.

Latent and productive viral infections are at the extremes of the spectrum of virus-cell interactions that are thought to play a major role in the ability of such important human pathogens as human immunodeficiency virus (HIV) to elude host defenses and cause disease. The recent development of PCR-based methods to amplify target sequences in individual cells in routinely fixed tissues affords opportunities to directly examine the subtle and covert virus-cell relationships at the latent end of the spectrum that are inaccessible to analysis by conventional in situ hybridization techniques. We have now used PCR in situ with in situ hybridization to document latent and permissive HIV infection in routinely fixed and paraffin-embedded tissue. In one of the first specimens we examined, a tumor biopsy from an HIV-infected individual, we found many of the lymphocytes and lymphocytes infiltrating the tumor had HIV DNA that was detectable only by PCR in situ. The fraction of positive cells varied regionally, but there were foci where most of the cells contained HIV DNA. Most of these lymphocytes and macrophages are latently infected, as we could detect HIV RNA in fewer than one in a thousand of these cells. We also detected HIV RNA, surprisingly, in 6% of the tumor cells, where the number of copies of viral RNA per cell was equivalent to productively infected cell lines. The alternative states of HIV-gene expression and high local concentration of latently infected lymphocytes and monocytes revealed by these studies conceptually supports models of lentiviral pathogenesis that attribute persistence to the reservoir of latently infected cells and disease to the consequences of viral-gene expression in this population. The magnitude of infection of lymphocytes documented in this report is also consistent with the emerging view that HIV infection per se could contribute substantially to depletion of immune cells in AIDS.

Activation of infectious virus from latent human immunodeficiency virus infection of monocytes in vivo.

Individuals infected with HIV may be asymptomatic for years before progressing to overt AIDS. Since HIV can latently infect monocytoid cell lines, we examined whether HIV latency occurs in monocytes in vivo. Freshly isolated monocytes from asymptomatic seropositive individuals examined before and after culture were positive for HIV DNA, but not RNA, as measured by polymerase chain reaction, showing that HIV latency occurs in monocytes in vivo. Coculture of these latently infected monocytes with Con A-activated T cells from HIV-negative normal donors stimulated 90% of the patients' samples and latently infected THP-1 to produce infectious virus. Neither Con A, resting T cells, nor T cell supernatants induced virus. Plasma membranes from activated T cells stimulated HIV production, suggesting cell contact induces factor(s) in monocytes to overcome latency. Thus, monocytes in AIDS patients harbor latent HIV inducible during an immune response, leading to T cell infection and viral-induced pathology.

Absence of human immunodeficiency virus (HIV) proviral sequences in seronegative hemophilic men and sexual partners of HIV-seropositive hemophiliacs.

To detect latent infection with human immunodeficiency virus (HIV), specimens of peripheral blood leukocytes from HIV-seronegative hemophiliacs and from sexual partners of HIV-seropositive hemophiliacs were examined by polymerase chain reaction (PCR). The primer pair SK 38/39 derived from the gag region and/or the primer pair SK 68/69 corresponding to a conserved region of the env gene were used. Whereas HIV proviral DNA was detected by PCR in samples from 86 (97%) of 89 HIV-seropositive hemophiliacs, no HIV-DNA was found in blood samples of 198 HIV-seronegative hemophiliacs at risk. Of 40 HIV-seronegative sexual partners of HIV-infected hemophiliacs, none was PCR positive. Thus, PCR is proving to be a sensitive method by which to confirm infection in seropositive hemophiliacs, while the negative results in HIV-seronegative hemophiliacs and HIV-seronegative sexual partners of HIV-seropositive hemophiliacs suggest that a prolonged seronegative period of latent HIV infection is the exception.

Morphine-Induced Transactivation of HIV-1 LTR in Human Neuroblastoma Cells

Infection by human immunodeficiency virus (HIV) is followed in many cases by a clinically quiescent or latent phase that appears to continue as long as host antiviral defense is intact. This has raised the possibility that certain host susceptibility factors (i.e., environmental cofactors) might influence the progression of the disease. In this study we demonstrate that morphine can function to activate HIV/LTR-CAT fusion gene (HIV-long terminal repeat-chloramphenicol acetyltransferase) when transfected into undifferentiated human SH-SY5Y neuroblastoma cells. The stimulatory effect of morphine is amplified in SH-SY5Y cells that have been induced to differentiate first with phorbol 12-myristate 13-acetate (PMA) and is much less in cells differentiated with retinoic acid (RA). Morphine does not appreciably activate HIV/LTR-CAT expression in human MOLT-3 and other T cells. Morphine activation of HIV/LTR-CAT in the SH-SY5Y cells is not reversible by naltrexone and appears to involve a Fos/Jun signaling system. Our results suggest that narcotics such as morphine may lead to activation of latent HIV infection. This may be particularly important in tissues, such as brain, which can host latent HIV infection and which is uniquely damaged in patients with acquired immunodeficiency syndrome (AIDS) as evidenced by neuronal degeneration and dementia. We also predict that these findings may have important implications for the pathogenesis of AIDS, particularly in opiate drug abusers.

Expression of human immunodeficiency virus long terminal repeat in the human promonocyte cell line U937: Effect of endotoxin and cytokines

Phagocytic macrophages are known to support noncytopathic, chronic infections of human immunodeficiency virus (HIV). Regulation of viral replication in such cells with either chronic low-grade or latent HIV infection is probably influenced by both viral and cellular factors acting on the viral long terminal repeat (LTR). This study identifies naturally occurring biological response modifiers which are able to affect the HIV-LTR linked to the chloramphenicol acetyl transferase (LTR-CAT) gene in a stable transfection of the human promonocyte cell line, U937, in the absence of other viral proteins. In this model system, endotoxin lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) are able to independently stimulate expression of LTR-CAT. Granulocyte/macrophage-colony-stimulating factor can enhance the effect of TNF-α or LPS, but other cytokines tested had minimal or no effect on LTR-CAT. In addition to effects on cellular susceptibility and immune function, the ability of naturally occurring factors to affect HIV-LTR in its integrated state may have particular relevance to progression of active disease from latent infection.

Antigenic epitopes of NEF proteins from different HIV-1 strains as recognized by Sera from patients with manifest and latent HIV infection

Human immunodeficiency virus (HIV) infection that generally causes a strong antibody response toward HIV may sometimes occur in a latent form, characterized by seronegativity in assays based on structural HIV proteins. Latently infected individuals, however, often have an antibody response against the nonstructural regulatory HIV-1 protein NEF, a factor implicated in down-regulation of viral expression. In order to define the specificity of NEF antibodies, we looked for antibody response against more than 600 overlapping nonapeptides representing the total NEF sequence of three different HIV-1 isolates BRU, SF2, and MAL. Nine distinct homologous antigenic epitopes were recognized by sera from seropositive HIV-1-infected individuals by the peptide ELISA. We further demonstrated that sera from “at risk” individuals, with no antibodies to HIV structural proteins but reacting with the recombinant NEF protein in Western blot, recognize the same epitopes. Immunological assays based on the defined NEF epitopes can therefore be used to diagnose early or latent HIV infection.

Effects of alcohol ingestion on in vitro susceptibility of peripheral blood mononuclear cells to infection with HIV and of selected T-cell functions.

A role for the biological effects of alcohol is postulated in the increased risk of AIDS known to be associated with chronic alcohol abuse and alcohol consumption during sexual activity. In pilot experiments peripheral blood mononuclear cells from healthy volunteers were studied before and after a single ingestion of 0.7 to 3.1 liters of beer or an equivalent dose of ethanol in other beverages. After moderate alcohol consumption there was increased human immunodeficiency virus (HIV) replication in peripheral blood mononuclear cells during 28 days of culture without mitogen stimulation as indicated by overnight syncytium formation with SUP-T1 indicator cells and by increased levels of HIV p24 antigen in the culture supernates. There was also decreased ability of lymphocytes to produce interleukin 2 and soluble immune response suppressor activity after stimulation with concanavalin A, the former, possibly both, for over 4 days after alcohol ingestion. These preliminary data extend well-known immunosuppressive effects of chronic alcohol ingestion to acute ingestion and raise the question: Could even casual alcohol consumption enhance HIV infectivity and/or enhance the progression of latent HIV infection?

Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B.

Binding of peptide hormones to surface membrane receptors leads to the transcription of specific genes within relevant target cells. How these signals are transduced to alter gene expression is largely unknown, but this mechanism probably involves a sequence of enzymatic steps that activate factors in the nucleus that modulate transcription. We now demonstrate that two different peptide hormones, or cytokines, stimulate the human immunodeficiency virus enhancer, and this effect is mediated by nuclear factor (NF) kappa B (nuclear factor that binds the kappa immunoglobulin light chain gene enhancer). These cytokines, tumor necrosis factor alpha and interleukin 1, act on multiple cell types and represent the only naturally occurring activators of this transcription factor among eight cytokines examined. Although NF-kappa B binding can be stimulated by phorbol 12-myristate 13-acetate, tumor necrosis factor alpha acts through an independent mechanism, inducing NF-kappa B binding in HT-2 cells, which did not show increased binding in response to phorbol 12-myristate 13-acetate, and causing superinduction in Jurkat T-lymphoma cells. Tumor necrosis factor alpha is also a more selective activator of T cells than phorbol 12-myristate 13-acetate, having no effect on lymphokine production in EL-4 cells at the same time it induces NF-kappa B. These findings suggest that human immunodeficiency virus gene expression can be induced in T cells without activating lymphokine secretion and that the role of these cytokines in the activation of latent human immunodeficiency virus infection deserves further clinical evaluation. Finally, this link between binding at the surface membrane and stimulation of a specific transcription factor should help define intermediates for these cytokine activation pathways.

LONG LATENCY PRECEDES OVERT SEROCONVERSION IN SEXUALLY TRANSMITTED HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

Signs of latent HIV infection were sought in stored serum samples collected before overt seroconversion, confirmed by enzyme-linked immunosorbent assay (ELISA), from 9 subjects with human-immunodeficiency-virus (HIV) infection, in serum from 25 seronegative sexual partners of HIV-seropositive men and from 23 other seronegative, homosexually active men. Free HIV antigen and/or low-titre antibodies to recombinant structural (core, env) or non-structural (3'orf, sor, tat) proteins were seen 6-14 months before seroconversion in all 9 subjects who seroconverted. Antibodies against core proteins detected by western blot were usually the first sign of latent HIV infection. 5 of the 25 ELISA-negative exposed partners have shown HIV antigenaemia and antibodies against core proteins for 16-34 months. By in-situ hybridisation, HIV-specific RNA was detected in peripheral-blood non-lymphoid mononuclear cells in some of the latently infected partners. All subjects with latent HIV infection had normal numbers of T4 lymphocytes but half of them lost their in-vitro proliferative T-cell response to a recall antigen (purified protein derivative of tuberculin). Early HIV infection, characterised by a low-level and restricted antibody response towards HIV core and regulatory proteins, seems mainly to affect antigen-presenting cells.

Human immunodeficiency virus infection of the developing human nervous system

Human immunodeficiency virus (HIV), the etiologic agent of acquired immune deficiency syndrome (AIDS) and AIDS-related complex, has recently been implicated as a factor in the development of AIDS-related neurologic dysfunction and may be responsible for an increasing number of neonatal immunologic and neurologic disorders. However, as yet there is no model system available to investigate the interaction of HIV with the developing human nervous system in vitro. To approximate the intracellular events associated with HIV infection of the human fetus nervous system we infected cells obtained by enzymatic dissociation of aborted human fetus dorsal root ganglia and their attached spinal roots and nerves. The expression of the HIV gag gene protein products (p17 and p24) was detected in a subpopulation of cells with a nonneuronal morphology, reaching a maximum within 3 days. Although 70% of the nonneuronal cells were p17- and p24-positive 3 days after infection, a majority of the cell population survived acute HIV infection, with the expression of p17 and p24 decreasing below the limit of detection by 12 days postinfection. This system may prove useful for examining the neuropathology and neurobiology of acute, persistent, or latent HIV infection of the developing human nervous system.