Miles Cloyd

University of Texas Medical Branch at Galveston | UTMB · Department of Microbiology and Immunology

NK cells play an important role in innate immunity to mycobacteria and are a significant source of the bactericidal effector molecule granulysin. Defects in NK cells have been described in HIV-infected patients, though mechanistic studies have focused on effector molecules relevant to anti-viral, and not anti-bacterial, function. Here we used prima...

Recently, there is considerable interest in the field of anti-HIV therapy to identify and develop chromatin-modifying histone deacetylase (HDAC) inhibitors that can effectively reactivate latent HIV in patients. The hope is that this would help eliminate cells harboring latent HIV and achieve an eventual cure of the virus. However, how effectively...

The clinical significance of persistent residual viremia in patients on prolonged highly active antiretroviral therapy (HAART) is not clear. Moreover, it remains to be demonstrated whether residual viremia consists of viruses capable of spreading infection in vivo upon termination of therapy. Using residual viral RNAs (vRNAs) isolated from a HAART-...

Immunosuppression following infection with HIV-1 predisposes patients to a myriad of opportunistic pathogens, one of the most important of which is Mtb. Granulysin, expressed by NK cells and CTL, exhibits potent antimicrobial activity against Mtb and several other opportunistic pathogens associated with HIV-1 infection. The immune signals that prom...

The establishment and persistence of many chronic infections have been demonstrated to depend on restraint of the vigor of the anti-microbial immune responses by CD4+CD25+ regulatory T (Treg) cells. In HIV-infected individuals, Treg cells suppress both HIV-specific and general CD4+ and CD8+ T cell responses. Increases of CD4+CD25+ Treg cell functio...

The cellular source(s) and the clinical significance of persistent low-level viremia, below 50 HIV RNA copies per ml of plasma, achieved in many patients with high adherence to highly active antiretroviral therapy (HAART) remain unclear. Also, it is not clear if residual plasma HIVs during HAART can become predominant populations in the rebounding...

The hallmark of HIV-1 disease is the gradual disappearance of CD4+ T cells from the blood. The mechanism of this depletion, however, is still unclear. Evidence suggests that lymphocytes die in lymph nodes, not in blood, and that uninfected bystander cells are the predominant cells dying. Our and others' previous studies showed that the lymph node h...

Studies of mechanisms of HIV-latency and its reactivation in long-lived resting CD4+ T-lymphocytes in patients have been limited due to the very low frequency of these cells ( approximately 1-10 cells per 10(6) CD4+ T-cells). To circumvent this obstacle, an in vitro culture system for post-activation long-term survival of normal CD4+ T-cells in a q...

Very early detection of HIV infection could help decrease the spread of HIV, improve safety of the blood supply, and permit earlier treatment. Early detection was reported when native gp41 antigen was used to detect antibodies that occurred 2-6 weeks earlier than detection of antibodies to denatured antigens by the current EIA or WB tests or detect...

In HIV-infected patients, increased levels of IL-10, mainly produced by virally infected monocytes, were reported to be associated with impaired cell-mediated immune responses. In this study, we investigated how HIV-1 induces IL-10 production in human monocytes. We found that CD14(+) monocytes infected by either HIV-1(213) (X4) or HIV-1(BaL) (R5) p...

Evidence of transient HIV infections was found in 8 subjects at high-risk for HIV infection among 47 longitudinally studied over 2-5 (average approximately 3.5) years, whereas only two subjects developed progressive infection. All of these subjects developed serum antibodies (Ab) to conformational epitopes of HIV gp41 (termed "early HIV Ab"), but t...

Certain safe over-the-counter (OTC) sexual lubricants such as Astroglide, KY Liquid, Replens, Vagisil, ViAmor, and Wet Stuff inhibit both cell-free HIV and the production of HIV by infected leukocytes in vitro even in the presence of seminal fluid. To identify which components of the lubricants were active against HIV, we tested five components (gl...

The mechanism(s) by which human immunodeficiency virus (HIV) causes depletion of CD4 lymphocytes remains unknown. Evidence has been reported for a mechanism involving HIV binding to (and signaling) resting CD4 lymphocytes in lymphoid tissues, resulting in up-regulation of lymph node homing receptors and enhanced homing after these cells enter the b...

On the basis of human immunodeficiency virus (HIV) needlestick studies, the time to seroconversion for anti-HIV antibodies is 1–9 months (mean, ∼2–3 months). However, an earlier marker of an immune response to HIV often occurs—serum anti-HIV antibodies reactive with live HIV-infected cells, termed “early HIV antibodies.” The specificities of these...

Understanding the dynamics of naive and memory CD4+ T cells in the immune response to HIV-1 infection can help elucidate typical disease progression patterns observed in HIV-1 patients. Although infection markers such as CD4+ T-cell count and viral load are monitored in patient blood, the lymphatic tissues (LT) have been shown to be an important vi...

During acute human immunodeficiency virus (HIV) infection, both virus load (HIV RNA) and infectivity are high (103-107 RNA copies/mL or TCID50/mL) until antibody is produced, which may reduce the HIV infectivity. In HIV carriers, the HIV RNA load is elevated (103–105 copies/ mL), but infectivity is low (100–102 TCID50/mL). The low infectivity in ca...

HIV infection causes an acquired immunodeficiency, principally because of depletion of CD4 lymphocytes. The mechanism by which the virus depletes these cells, however, is not clearly understood. Since the virus predominantly infects CD4 lymphocytes in vivo, some have assumed that HIV replication directly kills the infected cells or that the anti-HI...

HIV is transmitted to 6.4 million human beings per year and the majority of these transmissions are sexual. Condoms are highly effective and are recommended as the primary preventive. However, the fact that there are millions of sexual transmissions each year indicates that many people do not use condoms and that additional preventives are needed....

Several proposed theories have described the progression of HIV infection. Even so, no concrete evidence supports any as comprehensive, including, for example, why the CD4+ T-cell counts fall from 1000/mm^3 of blood to roughly 100/mm^3 over an average 10-year period, whereas concomitant viral loads are relatively constant, increasing by several or...

The mechanism by which HIV causes depletion of CD4+ T cells in infected individuals remains unknown. Numerous theories have been proposed, but none can fully explain all of the events observed to occur in patients. Recent studies have shown that HIV binding to resting CD4+ T cells upregulates L-selectin, causing the cells to home from the blood int...

Salivary transmission by the 30 million human immunodeficiency virus (HIV) carriers is rare, despite kissing, aerosolization, and dental treatment. The main protective mechanism of saliva is reported to be inactivation of HIV-transmitting leukocytes by its unique hypotonicity; however, the successful oral transmission of HIV by seminal fluid and mi...

The mechanism by which HIV causes depletion of CD4 lymphocytes remains unknown. Recent studies have demonstrated that HIV binding to resting CD4 lymphocytes causes them to home from the blood into lymph node, and during the homing process, they are induced into apoptosis only to secondary signals through the homing receptors. If this is the princip...

Oral transmission of human immunodeficiency virus (HIV) by the millions of HIV-infected individuals is a rare event, even when infected blood and exudate is present. Saliva of viremic individuals usually contains only noninfectious components of HIV indicating virus breakdown. To determine whether unknown HIV inhibitory mechanisms may explain the a...

Recently, we reported that abortive HIV infection of resting human T lymphocytes up-regulated expression of CD62L, the receptor for homing to lymph nodes (LNs), and enhanced homing of these cells from the blood into the LNs (Wang et al., 1997, Virology 228:141). This suggested that HIV-induced homing of resting lymphocytes (which comprise >98% of a...

In vitro infection of PHA-stimulated, normal CD4+ human peripheral blood T lymphocytes (PBLs) with several HIV-1 isolates did not result in cytopathology, despite high levels of virus replication and the fact that some of these isolates were cytopathic in certain cell lines. In contrast, infection of unfractionated PBLs (containing CD8+ as well as...

Many patients with AIDS have a myelopathy characterized by vacuolization of spinal cord white matter. The biochemical and molecular changes underlying this myelin disturbance have not yet been characterized. Myelin basic protein (MBP) is potentially important because it is a key structural protein of myelin with roles in compaction and stabilizatio...

In patients with HIV encephalitis, activated macrophages and microglial cells in the brain are infected by the human immunodeficiency virus (HIV-1). Immune activation can release neurotoxic chemicals including cytokines, free radicals, autocoids, and hydrolytic enzymes. In this study, the presence of hydrolytic enzymes in acquired immune deficiency...

We have isolated a naturally arising human immunodeficiency type 1 (HIV-1) mutant containing a point mutation within the env gene. The point mutation resulted in complete loss of balanced splicing, with dominant production of aberrant mRNAs. The aberrant RNAs arose via activation of normally cryptic splice sites flanking the mutation within the env...

We characterized two human immunodeficiency virus type 1 (HIV-1) strains, HIVMCK and HIV213, which have different cytopathic effects in infected cells. HIV213 was highly cytopathic, whereas HIVMCK was not. Biological analyses of chimeric viruses from the cloned infectious DNAs of HIVMCK and HIV213 showed that the Vpu region was responsible for the...

In vivo infection with human immunodeficiency virus type 1 (HIV-1) leads to gradual depletion of CD4+ T lymphocytes from the peripheral blood and later from the lymphoid organs. The mechanism of CD4 cell depletion is not known. HIV can only replicate in dividing lymphocytes, but greater than 98% of the lymphocytes in vivo at any given time are rest...

N-(4-Hydroxyphenyl)retinamide (4-HPR), a synthetic retinoic acid derivative, has chemopreventive effects on several types of cancer. We recently showed that 4-HPR is a potent inducer of apoptosis in malignant, but not normal, T-lymphoid cells in vitro. To test 4-HPR's effect in vivo, we used the virus-induced T-lymphoma in AKR/J mice as a model sys...

Most CD4+ lymphocytes in lymph nodes of both asymptomatic HIV-1-infected individuals and AIDS patients are nonproductively or latently infected. It is not clear how these cells come about because infection of resting lymphocytes results in abortive infection and infection of activated lymphocytes results in productive infection. The frequency and m...

CEM T-cells chronically infected with most HIV-1 isolates gradually cease virus production over a 4-6 week period. This is due to slow shutdown of virus replication in the majority of the cells, leading to latent infections. We identified one HIV-1 isolate (HIV213) which shut down into latency at a rate much slower than most HIV strains, requiring...

Expansion of the cerebral ventricles is highly prevalent in patients with the acquired immunodeficiency syndrome (AIDS). The mechanism remains unclear. The purpose of this study was to correlate the volume of the cerebral ventricles with histopathologic abnormalities in the brain. At autopsy, the volume of the cerebral ventricles in brain slices wa...

Similar to other vertebrate animals, humans possess retroviruses that exist in two forms: as normal genetic elements in their chromosomal DNA (endogenous retroviruses) and as horizontally-transmitted infectious RNA-containing viruses which are transmitted from human-to-human (exogenous retroviruses, e.g. HIV and human T cell leukemia virus, HTLV)....

Ecotropic recombinant virus (ERV), a relatively new class of murine retrovirus endogenous to mice, is expressed at significant levels by most murine myeloma and hybridoma cells examined. The routine XC, S+L-, mink cell focus-inducing (MCF), and reverse transcriptase (RT) tests are not suitable to detect and quantify the levels of ERV. A serological...

Unstimulated whole saliva was collected from 21 HIV-positive men and women before and after dental treatment. The frequency of HIV detection did not increase after dental treatment. Infectious HIV was recovered from only one patient. Study findings raise the possibility that, in most cases, salivary inhibitors render the virus non-infectious.

We examined the effect of chronic human immunodeficiency virus 1 (HIV-1) infection on the growth of human leukemic CEM T cells exposed to compounds which act through several major hormone or hormone-like signal transduction systems. Three were not altered by HIV-1 infection. Micromolar 8-bromo-cAMP inhibited cell growth equally in uninfected and in...

We examined the effect of chronic human immunodeficiency virus 1 (HIV-1) infection on the growth of human leukemic CEM T cells exposed to compounds which act through several major hormone or hormone-like signal transduction systems. Three were not altered by HIV-1 infection. Micromolar 8-bromo-cAMP inhibited cell growth equally in uninfected and in...

Naturally occurring recombinant murine leukemia viruses (MuLVs), termed mink cell focus-inducing (MCF) viruses, are the proximal leukemogens in spontaneous thymic lymphomas of AKR mice. The mechanism by which these viruses transform lymphocytes is not clear. Previous studies have implicated either integrational activation of proto-oncogenes, chroni...

The FDA-approved tests for diagnosis of HIV exposure depend on detection of specific antibody in serum. HIV infection is missed in some individuals because they score seronegative by the standard clinical EIA and Western blot assays. This apparent immunological "silent" period following infection may last for months and has been reported to be as l...

Independent isolates of HIV-1 differ widely in their tropisms for CD4-positive T-cell lines. This study demonstrates that tropisms of 10 different HIV-1 isolates also differ widely, as much as 1000-fold, for normal peripheral blood lymphocytes (PBLs) cultured from any given donor. This could only be reproducibly demonstrated by end point titrations...

Cytopathic viruses injure cells by a number of different mechanisms. The mechanism by which HIV-1 injures T cells was studied by temporally examining host-cell macromolecular syntheses, stages of the cell cycle, and membrane permeability following acute infection. T cells cytopathically infected at an m.o.i. of 1-5 grew normally for 24-72 hr, depen...

The ability of cells infected with a retrovirus to interfere with superinfection by another retrovirus usually involves blockage, by the primary virus, of the receptors for the superinfecting virus. Retroviruses using different receptors do not interfere with each other, and this property has been used to classify various types of retroviruses. Dif...

In vitro assessment of biological properties of 14 independent isolates of human immunodeficiency virus type 1 (HIV-1) was performed in order to gain insight into the spectrum of behavioral diversity of HIV-1s and to attempt to identify phenotypic traits that may be eventually correlated with in vivo pathogenesis. All of these biologically cloned i...

Details of the molecular interactions between human immunodeficiency virus (HIV-1) and its host cell during the infection process are not entirely clear. Building on recent reports by Lehr and Zimmer (1986, DMW 111, 1001-1002) that the membrane-reactive, anti-epileptic drug diphenylhydantoin (dilantin or phenytoin) (PHT) inhibited binding of HIV to...

Following injury or activation in some immune cell lines, elevation of intracellular Ca2+ concentration (Cai2+) is an early and major event that precedes cell death. Agents shown to elevate Cai2+ and to result subsequently in the death of some cells include human immunodeficiency virus (HIV) (in T4+ cells), 25-hydroxy cholesterol, tumor necrosis fa...

The molecular mechanism(s) by which human immunodeficiency virus (HIV-1) injures a T-cell line was studied. A pathological role for viral env proteins, which are inserted into the plasma membrane, has been previously demonstrated for HIV as well as other retroviruses which are cytopathic. We therefore initiated studies examining whether perturbatio...

We examined the antigens of human immunodeficiency viruses (HIV) expressed on infected H9 cells using live-cell membrane immunofluorescence and immunofluorescence absorption. Application of this nondenaturing serological method permitted analysis of HIV antigenic determinants maintained in their native configurations on the cell surface. Sera from...

Sixteen mouse and rat monoclonal antibodies reactive with gag or env proteins of Friend murine leukemia virus (F-MuLV) or recombinant MCF viruses related to F-MuLV were derived. Specificity of these was determined by immunofluorescence, immunoprecipitation, and reactivity with viral proteins blotted onto nitrocellulose paper. Seven antibodies react...

The effect of cell surface gp70 expression on reinfection by murine leukemia virus was studied in Friend virus (FV)-induced erythroleukemia cell clones. A clone (2C) which released gp70-positive infectious virions and expressed large amounts of cell surface ecotropic FV gp70 was not superinfectable by ecotropic viruses, whereas another clone (7C) w...

Monoclonal antibodies were derived from hybrid cell lines produced by fusing mouse myeloma cells with spleen cells from mice recovering from Friend virus-induced erythroleukemia. Of the 17 clones characterized, two appeared to have the Friend, Moloney, Rauscher pattern of specificity. One of these was specific for the envelope protein, gp70, and th...