Targets For HIV Infection Research Articles

Special Lecture

HIV epidemic is still growing at rapid rates, with more than 34 million people living with HIV and 1.8 million AIDS-related deaths last year, according to UNAIDS/WHO. The main route for HIV spread is HIV sexual/mucosal transmission with 2.7 million newly infected individuals every year. Prevention by novel interventions during the very earliest stages of transmission offers one of the best hopes of making a significant impact in this alarming epidemic. Indeed, mass distribution of antiretrovirals is difficult to achieve and a highly effective anti-HIV vaccine will not be available in the near future. Therefore, understanding the mechanisms of HIV-1 mucosal transmission represents an essential step towards creating novel opportunities to control HIV propagation. Dendritic cells (DCs) including Langerhans cells (LCs) are likely to be among the earliest targets of HIV infection. Our studies aim to decipher the complex interactions of HIV with DCs/LCs with the goal in mind to offer perspectives for understanding HIV transmission and pathogenesis and should contribute to the search for novel microbicides or other HIV preventions and therapies. We will review here the multifaceted roles of dendritic cells and Langerhans cells in viral infections including HIV-1. We will also discuss some of the clinical manifestations of HIV infection including skin manifestations such as chronic herpes infections, eosinophilic folliculitis and discuss the immune reconstitution syndrome.

Targets for HIV-1 infection in the human uterine mucosa during the first trimester pregnancy and control of transmission

Targets for HIV-1 infection in the human uterine mucosa during the first trimester pregnancy and control of transmission

Do Opioids Activate Latent HIV-1 by Down-Regulating Anti-HIV microRNAs?

Researchers have recently demonstrated the presence of anti-HIV-1 microRNAs (miR-28, miR-125b, miR-150, miR-223, and miR-382) in monocytes, macrophages, and CD4+ T cells, which are the primary targets of HIV infection. These miRNAs appear to regulate the level of infectivity of HIV-1 in the target cells, and thus have an impact on HIV-1 latency. The levels of these miRNAs are significantly higher in resting CD4+ T cells than those in active CD4+ T cells, whereas HIV-1 infectivity is greater in active than in resting CD4+ T cells. Similarly, the levels of these miRNAs are significantly higher in monocytes than in macrophages, whereas HIV-1 infectivity is greater in macrophages than in monocytes. Down-regulation or inhibition of the activity of these miRNAs can promote replication of latent HIV-1 in resting CD4+ T cells and in monocytes. Recently, morphine was shown to down regulate the expression of anti-HIV miRNAs (miRNA-28, 125b, 150, and 382) in cultured human monocytes and this effect of morphine was mediated via activation of mu opioid receptors (MOR). In addition, levels of these anti-HIV miRNAs were significantly lower in the peripheral blood mononuclear cells (PBMCs) isolated from heroin-dependent subjects than those from control subjects. These findings raise an important question: Does morphine have potential to activate latent HIV-1 in resting CD4+ T cells and macrophages, including microglia of human subjects maintained on highly active antiretroviral therapy (HAART)? Further research is required to answer this question.

Epigenetic Regulation of Tumor Necrosis Factor α (TNFα) Release in Human Macrophages by HIV-1 Single-stranded RNA (ssRNA) Is Dependent on TLR8 Signaling

Human macrophages at mucosal sites are essential targets for acute HIV infection. During the chronic phase of infection, they are persistent reservoirs for the AIDS virus. HIV virions gain entry into macrophages following ligation of surface CD4-CCR5 co-receptors, which leads to the release of two copies of HIV ssRNA. These events lead to reverse transcription and viral replication initiation. Toll-like receptors TLR7 and TLR8 recognize specific intracellular viral ssRNA sequences, but in human alveolar macrophages, their individual roles in TLR-mediated HIV ssRNA recognition are unclear. In the current study, HIV-1 ssRNA induced TNFα release in a dose-dependent manner in adherent human macrophages expressing both intracellular TLR7 and TLR8. This response was reduced by inhibiting either endocytosis (50 μm dynasore) or endosomal acidification (1 μg/ml chloroquine). Either MYD88 or TLR8 gene knockdown with relevant siRNA reduced HIV-1 ssRNA-mediated TNFα release, but silencing TLR7 had no effect on this response. Furthermore, HIV-1 ssRNA induced histone 4 acetylation at the TNFα promoter as well as trimethylation of histone 3 at lysine 4, whereas TLR8 gene knockdown reduced these effects. Taken together in human macrophages, TLR8 binds and internalizes HIV ssRNA, leading to endosomal acidification, chromatin remodeling, and increases in TNFα release. Drugs targeting macrophage TLR8-linked signaling pathways may modulate the innate immune response to acute HIV infection by reducing viral replication.

The Colocalization Potential of HIV-Specific CD8+ and CD4+ T-Cells is Mediated by Integrin β7 but Not CCR6 and Regulated by Retinoic Acid

CD4+ T-cells from gut-associated lymphoid tissues (GALT) are major targets for HIV-1 infection. Recruitment of excess effector CD8+ T-cells in the proximity of target cells is critical for the control of viral replication. Here, we investigated the colocalization potential of HIV-specific CD8+ and CD4+ T-cells into the GALT and explored the role of retinoic acid (RA) in regulating this process in a cohort of HIV-infected subjects with slow disease progression. The expression of the gut-homing molecules integrin β7, CCR6, and CXCR3 was identified as a “signature” for HIV-specific but not CMV-specific CD4+ T-cells thus providing a new explanation for their enhanced permissiveness to infection in vivo. HIV-specific CD8+ T-cells also expressed high levels of integrin β7 and CXCR3; however CCR6 was detected at superior levels on HIV-specific CD4+ versus CD8+ T-cells. All trans RA (ATRA) upregulated the expression of integrin β7 but not CCR6 on HIV-specific T-cells. Together, these results suggest that HIV-specific CD8+ T-cells may colocalize in excess with CD4+ T-cells into the GALT via integrin β7 and CXCR3, but not via CCR6. Considering our previous findings that CCR6+CD4+ T-cells are major cellular targets for HIV-DNA integration in vivo, a limited ability of CD8+ T-cells to migrate in the vicinity of CCR6+CD4+ T-cells may facilitate HIV replication and dissemination at mucosal sites.

Challenging New Targets for CNS–HIV Infection

The central nervous system (CNS) represents an important target for HIV infection during multiple stages of the disease: early, after invasion of the host, acting as a viral reservoir; lately, subverting its function and causing peripheral neuropathies and neurocognitive disorders; and lastly, during the final stage of NeuroAIDS, triggering opportunistic infections, cancers, and dementia. Highly active antiretroviral therapy, a combination of drugs that inhibits enzymes essential for HIV replication, can reduce the viremia and the onset of opportunistic infections in most patients, and prolong the survival. Among the limits of the current treatments the most noticeable is the inability to eradicate HIV-infected cells, both, limiting the time frame in which antiretroviral therapies initiated after exposure to HIV can prevent infection, and allowing replication-competent virus that persists in infected cells to emerge rapidly after the cessation of treatments. Many strategies are currently under evaluation to improve HIV treatment, unfortunately more than 98% of drug candidates for CNS disorders never make it to the clinic; here in we report how nanoformulated strategies might be adapted and applied to the field of CNS–HIV infection.

A Potential Role for Host-Microbe Dysbiosis in Enteropathy Associated with HIV Infection, Immune Complex Diseases

A Potential Role for Host-Microbe Dysbiosis in Enteropathy Associated with HIV Infection Human immunodeficiency virus (HIV) infection progressively depletes CD4+ T-lymphocytes from the immune system and, in the absence of treatment, leads to acquired immune deficiency syndrome (AIDS). Gut associated lymphoid tissue (GALT) harbors a majority of the body’s lymphocytes and is an early and important mucosal target of HIV infection. The massive and rapid depletion of CD4+ T cells from GALT in primary HIV infection is presumed to be an underlying cause of a progressive deterioration of intestinal immune and digestive functions collectively termed “enteropathy”. The most common clinical manifestations of HIV-associated enteropathy, diarrhea and malnutrition, have a devastating impact on the day-today lives of millions of patients world-wide.

Human HERC5 restricts an early stage of HIV-1 assembly by a mechanism correlating with the ISGylation of Gag

BackgroundThe identification and characterization of several interferon (IFN)-induced cellular HIV-1 restriction factors, defined as host cellular proteins or factors that restrict or inhibit the HIV-1 life cycle, have provided insight into the IFN response towards HIV-1 infection and identified new therapeutic targets for HIV-1 infection. To further characterize the mechanism underlying restriction of the late stages of HIV-1 replication, we assessed the ability of IFNbeta-induced genes to restrict HIV-1 Gag particle production and have identified a potentially novel host factor called HECT domain and RCC1-like domain-containing protein 5 (HERC5) that blocks a unique late stage of the HIV-1 life cycle.ResultsHERC5 inhibited the replication of HIV-1 over multiple rounds of infection and was found to target a late stage of HIV-1 particle production. The E3 ligase activity of HERC5 was required for blocking HIV-1 Gag particle production and correlated with the post-translational modification of Gag with ISG15. HERC5 interacted with HIV-1 Gag and did not alter trafficking of HIV-1 Gag to the plasma membrane. Electron microscopy revealed that the assembly of HIV-1 Gag particles was arrested at the plasma membrane, at an early stage of assembly. The mechanism of HERC5-induced restriction of HIV-1 particle production is distinct from the mechanism underlying HIV-1 restriction by the expression of ISG15 alone, which acts at a later step in particle release. Moreover, HERC5 restricted murine leukemia virus (MLV) Gag particle production, showing that HERC5 is effective in restricting Gag particle production of an evolutionarily divergent retrovirus.ConclusionsHERC5 represents a potential new host factor that blocks an early stage of retroviral Gag particle assembly. With no apparent HIV-1 protein that directly counteracts it, HERC5 may represent a new candidate for HIV/AIDS therapy.

HMGB1, an alarmin promoting HIV dissemination and latency in dendritic cells.

Dendritic cells (DCs) initiate immune responses by transporting antigens and migrating to lymphoid tissues to initiate T-cell responses. DCs are located in the mucosal surfaces that are involved in human immunodeficiency virus (HIV) transmission and they are probably among the earliest targets of HIV-1 infection. DCs have an important role in viral transmission and dissemination, and HIV-1 has evolved different strategies to evade DC antiviral activity. High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein that can act as an alarmin, a danger signal to alert the innate immune system for the initiation of host defense. It is the prototypic damage-associated molecular pattern molecule, and it can be secreted by innate cells, including DCs and natural killer (NK) cells. The fate of DCs is dependent on a cognate interaction with NK cells, which involves HMGB1 expressed at NK–DC synapse. HMGB1 is essential for DC maturation, migration to lymphoid tissues and functional type-1 polarization of naïve T cells. This review highlights the latest advances in our understanding of the impact of HIV on the interactions between HMGB1 and DCs, focusing on the mechanisms of HMGB1-dependent viral dissemination and persistence in DCs, and discussing the consequences on antiviral innate immunity, immune activation and HIV pathogenesis.

HIV-1 infection in polarized primary macrophages

Background Macrophages are important targets for HIV-1 infection and are involved in mucosal transmission of the virus. Due to their ubiquitous distribution, macrophages play a crucial role in virus spread and can become reservoirs for HIV-1. In vivo, macrophages are exposed to a multiplicity of signals that can polarize them into a classically activated M1 (IFN-g, LPS and/or TNF-a) or into alternatively activated M2a (IL-4, IL-13) and M2c (IL-10, glucocorticoids) phenotype. Previous studies have shown that the susceptibility of macrophages to HIV-1 infection is regulated by type I interferons (IFN-a, IFN-b) and by the cytokines IL-4 and IL-10, however the mechanism underlying the latter has not been described yet. In this study, the expression levels of HIV-1 restricting cellular factors in the different types of polarized monocyte-derived macrophages (MDM) was analyzed and their role in HIV-1 susceptibility was investigated.

Deregulation of microRNAs by HIV-1 Vpr leads to the development of neurocognitive disorders

Studies have shown that HIV-infected patients develop neurocognitive disorders that are marked by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1 infected target cells cause this neuronal deregulation. The viral protein R, a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells, however the mechanisms involved remain unclear. Using human neuronal cell line, we found that Vpr can be taken up by neurons causing i- deregulation of calcium homeostasis, ii- endoplasmic reticulum-calcium release, iii-activation of the oxidative stress pathway, iv- mitochondrial dysfunction and v- synaptic retraction. In search for the cellular factors involved, we performed microRNAs and gene array assays using human neurons (primary cultures or cell line, SH-SY5Y) that we treated with recombinant Vpr proteins. Interestingly, Vpr deregulates the levels of several miRNAs (e.g. miR-34a) and their target genes (e.g. CREB), which could lead to neuronal dysfunctions. Therefore, we conclude that Vpr is a major player in neuronal dysfunction through deregulating miRNAs and their target genes, a phenomenon that could lead to the development of HAND.

War and peace between WAP and HIV: role of SLPI, trappin-2, elafin and ps20 in susceptibility to HIV infection

Despite tremendous advances in our understanding of HIV/AIDS since the first cases were reported 30 years ago, we are still a long way from understanding critical steps of HIV acquisition, pathogenesis and correlates of protection. Our new understanding of the importance of the mucosa as a target for HIV infection, as well as our recent observations showing that altered expression and responses of innate pattern recognition receptors are significantly associated with pathogenesis and resistance to HIV infection, indicate that correlates of immunity to HIV are more likely to be associated with mucosal and innate responses. Most of the heterosexual encounters do not result in productive HIV infection, suggesting that the female genital tract is protected against HIV by innate defence molecules, such as antiproteases, secreted mucosally. The present review highlights the role and significance of the serine protease inhibitors SLPI (secretory leucocyte protease inhibitor), trappin-2, elafin and ps20 (prostate stromal protein 20 kDa) in HIV susceptibility and infection. Interestingly, in contrast with SLPI, trappin-2 and elafin, ps20 has been shown to enhance HIV infectivity. Thus understanding the balance and interaction of these factors in mucosal fluids may significantly influence HIV infection.

HIV Type 1 Genetic Variation in Foreskin and Blood from Subjects in Rakai, Uganda

The foreskin contains a subset of dendritic cells, macrophages, and CD4(+) and CD8(+) T cells that may be targets for initial HIV infection in female-to-male sexual transmission of HIV-1. We present analyses comparing HIV-1 sequences isolated from foreskin DNA and serum RNA in 12 heterosexual men enrolled in an adult male circumcision trial performed in Rakai, Uganda. Phylogenetic analysis demonstrated three topologies: (1) little divergence between foreskin and serum, (2) multiple genetic bottlenecks occurring in both foreskin and serum, and (3) complete separation of foreskin and serum populations. The latter tree topology provided evidence that foreskin may serve as a reservoir for distinct HIV-1 strains. Distance and recombination analysis also demonstrated that viral genotypes in the foreskin might segregate independently from the circulating pool of viruses.

CD4+ T lymphocyte reference values of immunocompetent subjects in an African university

CD4(+) T cells play critical roles in the immune system and, being primary targets of HIV infection, they are used to measure disease progression and response to combination antiretroviral therapy (cART), alongside other parameters, in HIV/AIDS patients. The aim of this study was to determine the reference values of CD4(+) T cells in a student population that was HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) negative. After ethical clearance and informed consent, 500 subjects (mean age = 26 years) were recruited, of whom 56 (11.2%) had HIV, HBV or HCV and were excluded. Blood samples were collected from the remaining 444 subjects into vacutainer tubes and analysed using the BD FACScount cytometer according to the manufacturer's instructions. Of the 444 subjects, 266 (59.9%) were male and 178 (40.1%) were female. The mean (± standard deviation) CD4(+) T cell count was 987 cells/µL (± 336). The mean counts among males and females were 957 cells/µL (± 306) and 991 cells/µL (± 340), respectively. Values of CD4(+) T cells ranged from 651 cells/µL to 1705 cells/µL. Subjects with higher CD4(+) T Cells were more likely to be female than male. There was no direct correlation between CD4(+) T cell values and age of the participants. Our findings offer the first insight into the CD4(+) T cell reference values of a Nigerian student population and provide useful data that will guide future cART decisions and other immune-based therapies.

Cellular phenotype impacts human immunodeficiency virus type 1 viral protein R subcellular localization

BackgroundHuman immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is a virion-associated regulatory protein that functions at several points within the viral life cycle and has been shown to accumulate primarily in the nucleus and at the nuclear envelope. However, most studies have investigated Vpr localization employing cell types irrelevant to HIV-1 pathogenesis. To gain a better understanding of how cellular phenotype might impact HIV-1 Vpr intracellular localization, Vpr localization was examined in several cell lines representing major cellular targets for HIV-1 infection within the peripheral blood, bone marrow, and central nervous system (CNS).ResultsUtilizing a green fluorescent protein-tagged Vpr, we detected Vpr mainly in foci inside the nucleus, at the nuclear envelope, and around the nucleoli, with dispersed accumulation in the cytoplasm of human endothelial kidney 293T cells. No differences were observed in Vpr localization pattern with respect to either the location of the tag (N- or C-terminus) or the presence of other viral proteins. Subsequently, the Vpr localization pattern was explored in two primary HIV-1 target cells within the peripheral blood: the CD4+ T lymphocyte (represented by the Jurkat CD4+ T-cell line) and the monocyte-macrophage (represented by the U-937 cell line). Vpr was found primarily in speckles within the cytoplasm of the Jurkat T cells, whereas it accumulated predominantly intranuclearly in U-937 monocytic cells. These patterns differ from that observed in a bone marrow progenitor cell line (TF-1), wherein Vpr localized mainly at the nuclear envelope with some intranuclear punctuate staining. Within the CNS, we examined two astroglioma cell lines and found that Vpr displayed a perinuclear and cytoplasmic distribution.ConclusionsThe results suggest that the pattern of Vpr localization depends on cellular phenotype, probably owing to interactions between Vpr and cell type-specific host factors. These interactions, in turn, are likely coupled to specific roles that Vpr plays in each cell type within the context of the viral life cycle. Phenotype-specific Vpr localization patterns might also provide an explanation with respect to Vpr secretion or release from HIV-1-infected cells within the peripheral blood and CNS.

Detection of Intraepithelial and Stromal Langerin and CCR5 Positive Cells in the Human Endometrium: Potential Targets for HIV Infection

Both the upper (endocervix and uterus) and lower (ectocervix and vagina) female genital tract mucosa are considered to be target sites for sexual transmission of HIV. There are a few reports on the T cell and antigen-presenting cell distribution in human endometrial tissue however, there is little known about the expression of the HIV co-receptor CCR5 and HIV-binding C-type lectin receptors on endometrial cell subsets. We therefore assessed endometrial tissue sections from HIV seronegative women undergoing hysterectomy of a benign and non-inflammatory cause for phenotypic characterization of potential HIV target cells and receptors by immunohistochemistry. Langerin was expressed on intraepithelial CD1a+CD4+ and CD11c+CD4+ Langerhans cells. Furthermore, CCR5+CD4+CD3+ T cells, DC-SIGN+MR+CD11c+ myeloid dendritic cells and MR+CD68+ macrophages were found within or adjacent to the epithelium of the uterine lumen. In addition, occasional CD123+ BDCA-2+ plasmacytoid dendritic cells were detected deep in the endometrial stroma. Both T cells and several antigen-presenting cells were detected in lymphoid aggregate formations in close proximity to the epithelial lining. The finding of intraepithelial and stromal Langerin+ cells as well as CCR5+ CD4+ T cells is novel for human endometrium.

A study of clinical profile of HIV positive patients with neurological manifestations

Background Central nervous system (CNS) is among the most frequent and serious target of HIV infection in patients with profound immunosuppression. CNS problems occur mainly due to either primary pathologic process of HIV or secondary to opportunistic infection and neoplasm. Aims and objectives To study the clinical and investigation profile in diagnosis of HIV patients with CNS manifestation. To correlate CD 4 levels with CNS opportunistic infections. Materials and methods A prospective observational non-randomized clinical study of 50 HIV infected patients, showing clinical evidence of CNS involvement, admitted in tertiary care centre was done. Detail clinical history and CNS examination was carried out. CD 4 count was measured using standard flowcytometry. Investigations like MRI brain/electromyography-nerve conduction studies/cerebrospinal fluid (CSF) examination were done as and when required for diagnosis. Results HIV induced primary CNS illness was present in 30% while 70% cases were due to secondary CNS manifestation mainly due to opportunistic infection. Most common primary illness was distal symmetric polyneuropathy (DSPN) (22%), followed by Aids dementia complex (ADC) (4%) and acute inflammatory demyelinating polyneuropathy (AIDP)(4%). tuberculous meningitis (TBM) was the most common presentation as secondary CNS illness (34%), followed by cryptococcal meningitis (14%), toxoplasmosis (10%), progressive multifocal leucoencephalopathy (PML) (8%) and neurosyphilis (4%). Meningitis was presenting CNS manifestation in majority of patients. The commonest presentation of TBM was fever (64%), while headache for cryptococcal meningitis (71%) and seizures was that of toxoplasmosis (80%). Mean CD 4 count was 170 ± 80.1 in patients of DSPN, 131 ± 85.75 for TBM, 47.5 ± 36.8 for cryptococcal, 160 ± 77.4 for toxoplasmosis and 93 ± 65 for ADC. Conclusion High degree of clinical suspicion of nervous involvement in HIV patients at all stages help in early diagnosis and institution of specific therapeutic measures which in turn decrease mortality and morbidity.

HIV Infection and Immune Defense of the Penis

Citation Anderson D, Politch JA, Pudney J. HIV infection and immune defense of the penis. Am J Reprod Immunol 2011; 65: 220–229Recent evidence that circumcision decreases HIV infection in heterosexual men by 50–60% has focused research on the foreskin as a target of HIV infection. In this review article, we discuss potential mechanisms underlying the circumcision effect and re‐examine the assumption that the foreskin is the principle penile HIV infection site. HIV target cells are present in the foreskin epithelium, but are also found in the epithelia of the penile shaft, glans/corona, meatus and urethral introitus. Sexually transmitted infections (STIs) can affect any of these sites and increase susceptibility to HIV acquisition by eroding the protective epithelial layer and by attracting and activating HIV target cells in the epithelium. The moist subpreputial cavity, which encompasses the entire penile tip in most uncircumcised men including the glans, meatus and urethral introitus, plays an important role in STI acquisition. Circumcised men have a lower rate of STIs that infect not only the foreskin but also other distal penile sites, especially the urethra. Likewise, the foreskin may trap HIV and HIV‐infected cells after intercourse thereby increasing the risk of HIV acquisition not only through the inner foreskin but also other sites covered by the foreskin. The subpreputial cavity also hosts a unique microbiome that may also play a role in HIV infection. We hypothesize that the penile urethra may be the primary HIV acquisition site in circumcised men and possibly also in non‐circumcised men because of the presence of superficial HIV target cells and a high incidence of STIs at this site. Both innate and adaptive immune defense mechanisms are operative in the lower male genital region. The penile urethral mucosa contains accumulations of IgA+ plasma cells and T lymphocytes and may provide a responsive target for future mucosal vaccines to prevent HIV sexual transmission.

β5 Integrin Is the Major Contributor to the αv Integrin-Mediated Blockade of HIV-1 Replication

Monocytes and macrophages are targets of HIV-1 infection and play critical roles in multiple aspects of viral pathogenesis. During the differentiation of monocytes to macrophages, adhesion molecules such as integrins are upregulated; therefore, they provide signals that control the process and subsequently may render macrophages more susceptible to HIV-1 infection. Previous work demonstrated that blocking α(v)-containing integrins triggered a signal transduction pathway leading to the inhibition of NF-κB-dependent HIV-1 transcription. In this paper, we show the influence of the different α(v)-coupled β integrins in HIV-1 replication in macrophages. Inhibition of β integrins, either by specific mAbs, small arginine-glycine-aspartic acid (RGD) mimetic compounds, or RNA interference, showed that integrin β(5) was the major contributor to the integrin-mediated blockade of HIV-1 replication. Importantly, such inhibition did not induce changes in cell adhesion to the substrate. In conclusion, our results reveal a significant role of the integrin dimer α(v)β(5) in HIV-1 infection of macrophages.

Distribution of HIV-1 Infection in Different T Lymphocyte Subsets: Antiretroviral Therapy-Naïve vs. Experienced Patients

Memory CD4 T cells are the primary targets of HIV-1 infection, which then subsequently spreads to other T lymphocyte subsets. Antiretroviral therapy (ART) alters the pattern of HIV-1 distribution. Blood samples were collected from ART-naïve or -experienced HIV-1 patients, and the memory and naïve subsets of CD4(+) and CD8(+) T lymphocytes, respectively, were isolated by cell sorting. DNA was extracted and the HIV-1 env C2/V3 region PCR amplified. Amplicons were cloned and sequenced, and genetic relatedness among different HIV-1 compartments was determined by the phylogenetic analysis of clonal sequences. The viral V3 sequence of HIV-1 in each compartment was analyzed by using webPSSM to determine CCR5 or CXCR4 coreceptor binding property of the virus. The direction of viral migration among involved compartments was determined by using the MacClade program. In ART-naïve patients, HIV-1 was generally confined to the memory CD4 T (mT4) cell compartment, even though in a few cases, naïve CD4 T (nT4) cells were also infected. When this occurred, the HIV-1 gene migrated from nT4 to mT4. In contrast, HIV-1 was detected in nT4 and mT4 as well as in the memory CD8 T (mT8) compartments of ART-experienced patients. However, no clear pattern of directional HIV-1 gene flow among the compartments could be determined because of the small sample size. All HIV-1-infected T cell compartments housed the virus that used either CCR5 or CXCR4 as the coreceptor.