Richard Noel

Ponce Health Sciences University · Department of Basic Sciences

Combination antiretroviral therapy (cART) targets viral replication, but early viral protein production by astrocytes may still occur and contribute to the progression of HIV-1 associated neurocognitive disorders and secondary complications seen in patients receiving cART. In prior work with our model, astrocytic HIV-1 Nef expression exhibits neuro...

The Research Centers in Minority Institutions (RCMI) Program was congressionally mandated in 1985 to build research capacity at institutions that currently and historically recruit, train, and award doctorate degrees in the health professions and health-related sciences, primarily to individuals from underrepresented and minority populations. RCMI...

Background: HIV-1-associated neurocognitive disorders (HAND) progression is related to continued inflammation despite undetectable viral loads and may be caused by early viral proteins expressed by latently infected cells. Astrocytes represent an HIV reservoir in the brain where the early viral neurotoxin negative factor (Nef) is produced. We prev...

Even though HIV-1 replication can be suppressed by combination antiretroviral therapy (cART) inflammatory processes still occur, contributing to comorbidities. Comorbidities are attributed to variety of factors, including HIV-1 mediated inflammation. Several HIV-1 proteins mediate central nervous system (CNS) inflammation, including Nef. Nef is an...

The Research Centers in Minority Institu­tions (RCMI) program was established by the US Congress to support the develop­ment of biomedical research infrastructure at minority-serving institutions granting doctoral degrees in the health professions or in a health-related science. RCMI institu­tions also conduct research on diseases that disproportio...

Alterations in soma, dendrites, and axon of a neuron as well as dysregulation of proteins and receptors can cause impaired function and be indicative of neurotoxicity. The microtubule associated protein-2 (MAP2) is a neuron-specific cytoskeletal protein that plays an important role in the development of processes, synaptic plasticity, and neuronal...

Astrocytes help to maintain neuronal function. The close relationship between neurons and astrocytes makes the latter a possible therapeutic target in neurological diseases. HIV-1 patients suffer neurocognitive impairments regardless of the efficacy of their antiretroviral therapy. In previous studies we have demonstrated that TGFβ and inflammatory...

Several HIV-1 proteins are pathogenic for cells without the need for active viral replication. This is the case of Nef, an early HIV-1 accessory protein, which causes learning impairment and damage to cells and tissues in our rat model of Nef neuropathology. There is also increased expression of Transforming Growth Factor beta (TGFb). We want to st...

The 23rd Scientific Conference of the Society on Neuroimmune Pharmacology (SNIP) will take place in Philadelphia, PA, USA, from March 29 to April 1, 2017. The conference will present a selection of the latest and most advanced research in the intersecting areas of neuroscience, immunology, pharmacology and its translational aspects.

The worldwide epidemic of HIV has been ameliorated with the development of antiretroviral therapies. Modern treatment has been efficient in impairing viral replication, resulting in an undetectable viral load in patients. Unfortunately, the process of viral protein production is still functional contributing to detrimental conditions such as HIV as...

Objective: HIV-1 variants with different tropisms are associated with various neuropathologies. This study intends to determine if this correlation is determined by unique viral env sequences. We hypothesize that HIV-1 envelope gene sequence changes are associated with cognition status. Methods: Viral RNA was extracted from peripheral blood mono...

Objective: Combined antiretroviral treatment (cART) has changed the clinical presentation of HIV-associated neurocognitive disorders (HAND) to that of the milder forms of the disease. Asymptomatic neurocognitive impairment (ANI) is now more prevalent and is associated with increased morbidity and mortality risk in HIV-1-infected people. HIV-1 enve...

The use and validity of the Graduate Record Examination General Test (GRE) to predict the success of graduate school applicants is heavily debated, especially for its possible impact on the selection of underrepresented minorities into science, technology, engineering, and math fields. To better identify candidates who would succeed in our program...

Milder forms of HIV-1 associated neurological disorders (HAND) represent one of the prevalent comorbidities that patients undergo in the current cART era. The viral protein Nef, a neurotoxin that causes learning deficiencies, is produced in the brain even when the virus is not detected. Our laboratory has published data from experiments done in an...

Neurocognitive impairments affect 30-50% of all HIV patients receiving antiretroviral treatment. Even when the therapy maintains viral loads under detectable levels, viral proteins such as Nef continue to be produced in distinct reservoirs. Our previous work with an animal model of Nef neurotoxicity suggests that TGFβ1 is linked to learning impairm...

HIV-1 infection can lead to neurocognitive impairment collectively known as HIV-associated neurocognitive disorders (HAND). Although combined antiretroviral treatment (cART) has significantly ameliorated HIV's morbidity and mortality, persistent neuroinflammation and neurocognitive dysfunction continue. This review focuses on the current clinical a...

Combined Antiretroviral Therapy (cART) reduces viral loads of HIV by preventing virus replication to slow down the progression to AIDS. Therapy does not prevent all viral gene expression and so morbidities continue to present in HIV infected people. HIV associated neurocognitive disorders (HAND) affect approximately 50% of HIV-1 positive individual...

HIV-infected individuals are at an increased risk of developing neurological abnormalities. HIV induces neurotoxicity by host cellular factors and individual viral proteins. Some of these proteins including viral protein R (Vpr) promote immune activation and neuronal damage. Vpr is known to contribute to cell death of cultured rat hippocampal neuro...

As the life expectancy of HIV-1 patients under treatment improves, mild forms of neuropathology have also increased. Controlling the replication of the virus does not prevent the production of early viral proteins such as Nef from latently infected cells including astrocytes. HIV infection and expression of Nef in astrocytes are each associated wit...

Neurocognitive impairments remain prevalent in HIV-1 infected individuals despite current antiretroviral therapies. It is increasingly becoming evident that astrocytes play a critical role in HIV-1 neuropathogenesis through the production of proinflammatory cytokines/chemokines. HIV-1 viral protein R (Vpr) plays an important role in neuronal dysfun...

The incidence of HIV-associated neurological disorders (HAND) has increased during recent years even though the highly active antiretroviral therapy (HAART) has significantly curtailed the virus replication and increased the life expectancy among HIV-1 infected individuals. These neurological deficits have been attributed to HIV proteins including...

Viral protein R (Vpr) is an accessory protein of HIV and SIV involved in the pathogenesis of viral infection. In this study, we monitored SIV evolution in the central nervous system and other organs from morphine-dependent and control animals by sequencing vpr in an attempt to understand the relationship between drug abuse, disease progression, and...

HIV is known to infect cells in the brain causing neurological impairments. Damage ranges from mild (HAND) to severe (HAD). We found learning impairment in rats infused with astrocytes expressing Nef. Histological studies performed on the brain tissues showed loss of neurons near the infusion site as well as evidence for TGFB signaling. We set up i...

Despite the widespread use of antiretroviral therapy that effectively limits viral replication, memory impairment remains a dilemma for HIV infected people. In the CNS, HIV infection of astrocytes leads to the production of the HIV-1 Nef protein without viral replication. Post mortem studies have found Nef expression in hippocampal astrocytes of pe...

Human endogenous retroviruses (HERVs) make up 8% of the human genome. The expression of HERV-K (HML-2), the family of HERVs that most recently entered the genome, is tightly regulated but becomes markedly increased after infection with HIV-1. To better understand the mechanisms involved in this activation, we explored the role of the HIV-1 Tat prot...

The majority of infection by the human immunodeficiency virus (HIV-1) across the world occurs by heterosexual transmission and is likely mediated by virus present in genital secretions. In spite of this, infection is followed by clinical markers of the virus present in blood, which may not be representative of the virus involved in transmission. In...

The majority of infection by the human immunodeficiency virus (HIV-1) across the world occurs by heterosexual transmission and is likely mediated by virus present in genital secretions. In spite of this, infection is followed by clinical markers of the virus present in blood, which may not be representative of the virus involved in transmission. In...

In addition to its role in virus entry, HIV-1 gp120 has also been implicated in HIV-associated neurocognitive disorders. However, the mechanism(s) responsible for gp120-mediated neuroinflammation remain undefined. In view of increased levels of IL-6 in HIV-positive individuals with neurological manifestations, we sought to address whether gp120 is...

Our previous studies have shown two distinct disease patterns (rapid and normal onset of clinical symptoms) in morphine-dependent SHIV/SIV-inoculated rhesus macaques. We have also shown that control as well as 50% of morphine-dependent macaques (normal progressor) developed humoral and cellular immune responses whereas the other half of the morphin...

The goal of this work is to use a lentivirus to create a simplified endogeonous expression system producing only Nef to study the unique contributions that this viral neurotoxin makes to HIV-related neurological impairment. We used PCR to generate the Nef gene flanked by unique restriction enzymes sites(BamH1 and Sal1). Then we digested a lentivira...

Human immunodeficiency virus-1 (HIV-1) and simian immunodeficiency virus (SIV) have been shown to compartmentalize within various tissues, including the brain. However, the evolution of viral quasispecies in the setting of drug abuse has not been characterized. The goal of this study was to examine viral evolution in the cerebral compartment of mor...

HIV and simian immunodeficiency virus (SIV) have a formidable capacity for mutation and adaptation, a characteristic that has contributed to the extensive genetic variability. Evolutionary pressures imposed within the host and the viral capacity to mutate lead to the generation of such variants. To date, very little information is available regardi...

Six morphine-dependent and three control macaques were infected with a mixture of SIV/SHIV. Half of the animals in the morphine group developed accelerated disease (rapid progressor) and died within 20 weeks postinfection. The evolution of the envelope gene in the brain of the rapid progressor and morphine-dependent group along with that in the con...

Both human immunodeficiency virus (HIV) and illicit drug addiction remain major health problems not only in the United States but all over globe. The effect of drug addiction on HIV/AIDS (acquired immunodeficiency syndrome) has been somewhat underexplored. However, in United States more than one fourth of HIV-positive individuals are injection drug...

A homeostatic balance exists between the cellular generation of oxidant species and endogenous antioxidants under normal physiological conditions. Human Immunodeficiency Virus (HIV) infection is known to affect this balance causing oxidative stress. However, the interaction of HIV infection with a substance abuse on cellular oxidant/antioxidant sys...

Oxidative stress is well documented in HIV infection, but the effect of concomitant substance abuse is largely unknown. We studied oxidative stress in our macaque model of morphine abuse and AIDS. In plasma, we found an approximately 50% decrease in catalase activity with morphine dependence that was exacerbated by infection in rapid progressors. S...

Three of six morphine-dependent monkeys progressed rapidly to AIDS and died by 20 weeks in our SIV/SHIV non-human primate model of drug addiction and AIDS. We studied the evolution of the SIV vpr gene in both cerebrospinal fluid (CSF) and plasma in these rapid progressors, in their normal progressor counterparts and in infected, drug-free controls...

We analyzed the association between the evolution of the V3-V5 regions of env and disease progression in our SIV/SHIV macaque model of morphine dependence and AIDS. Previous studies revealed two distinct disease patterns--fast progression and normal progression. To determine the effect of the two distinct patterns of disease in the evolution of SIV...

Six morphine-dependent and two control macaques were infected in an SIV/SHIV nonhuman primate model of AIDS. Three animals in the morphine group rapidly developed clinical disease and died within the timeframe of this study. The sequence evolution of nef in plasma virus was assessed at 4, 12, and 20 weeks postinfection. Cloned sequences were compar...

Morphine abuse has been associated with higher virus replication and accelerated disease progression in a non-human primate model of AIDS. In our previous report, we have shown that 50% of morphine-addicted macaques progress rapidly and that 2/3 of the rapid progressors exhibit severe neuropathogenesis. In this report, we examined the sequence evol...

We analyzed the association between evolution of the 5' exon of tat and disease progression in an SIV/SHIV macaque model of opiate dependence and AIDS. Cloned tat sequences were obtained by RT-PCR amplification of 3 plasma viruses (recovered at different times) from 6 morphine-dependent and 2 control Indian rhesus macaques inoculated with SHIV(KU-1...

Alcohol abuse constitutes a major cohort among HIV-infected individuals. The precise effect of alcohol addiction on HIV pathogenesis remains inconclusive, however. This study was designed to determine the effect of alcohol dependence on virus replication and CD4 profiles in simian immunodeficiency virus/simian-HIV-infected rhesus macaques. A group...

There is increasing evidence that male or female genital tract represent a distinct replication compartment for human immunodeficiency virus type 1 (HIV-1) and that such compartments may serve as a virus reservoir. Forty-four paired plasma and vaginal samples from HIV-infected females undergoing HAART were collected to examine the viral responses t...

Development of a drug-resistant variant of HIV-1 has been one of the major concerns contributing to the transmission of the virus. A 40-year-old woman presented to the clinic with micosis and oral candidiasis. The subject was referred for HIV-1 diagnosis. Subsequent investigations revealed a very low CD4 T cell count (48 cell/microl blood) and high...

In order to investigate the existing notion that the human immunodeficiency virus type 1 (HIV-1) infection in Puerto Rico (PR) was imported from the continental United States of America (USA) we sequenced and analyzed 900 bases of the HIV-1 pol sequence from individuals in PR for comparison with pol sequences from the USA mainland. The sequences we...