Loyda M Meléndez

University of Puerto Rico, Medical Sciences Campus · Department of Microbiology and Medical Zoology

Zika virus (ZIKV) compromises placental integrity, infecting the fetus. However, the mechanisms associated with ZIKV penetration into the placenta leading to fetal infection are unknown. Cystatin B (CSTB), the receptor for advanced glycation end products (RAGE), and tyrosine-protein kinase receptor UFO (AXL) have been implicated in ZIKV infection a...

Zika virus (ZIKV) infection has been associated with fetal abnormalities by compromising placental integrity, but the mechanisms by which this occurs are unknown. Flavivirus can deregulate the host proteome, especially extracellular matrix (ECM) proteins. We hypothesize that a deregulation of specific ECM proteins by ZIKV, affects placental integri...

HIV-associated neurocognitive disorders (HAND) are prevalent despite combined antiretroviral therapy (cART), affecting 52% of people living with HIV. Our laboratory has demonstrated increased expression of cathepsin B (CATB) in postmortem brain tissue with HAND. Increased secretion of CATB from in vitro HIV-infected monocyte-derived macrophages (MD...

Human immunodeficiency virus 1 (HIV-1) infects blood monocytes that cross the blood-brain barrier to the central nervous system, inducing neuronal damage. This is prompted by the secretion of viral and neurotoxic factors by HIV-infected macrophages, resulting in HIV-associated neurocognitive disorders. One of these neurotoxic factors is cathepsin B...

In spring of 2021, the Society on NeuroImmune Pharmacology (SNIP) organized a virtual workshop on the coronavirus disease 2019 (COVID-19). The daylong event’s fourth and final symposium, “Well-being and reflections,” offered a glimpse at the pandemic’s impact on the lives of our scientists and educators. This manuscript includes a brief summary of...

The respiratory disease caused by the Coronavirus infectious disease 2019 (COVID19) has spread rapidly since December 2019 in Wuhan, China. This new strain of Coronavirus is similar to the SARS Corona virus and has been termed SARS-CoV-2. Both viruses have emerged from bats and adapted to humans. On March 11, 2020 COVID19 was declared Pandemic by t...

Pathogenesis of HIV-associated neurocognitive disorders (HAND) is mediated through the infiltration of perivascular macrophages into the brain with the secretion of viral, neurotoxic and inflammatory proteins. One of these proteins is cathepsin B (CATB), a lysosomal cysteine protease that induces neuronal apoptosis, and increases in plasma and cere...

HIV-associated neurocognitive disorders prevail in 20–50 percent of infected individuals. Macrophages transmigrate through the blood brain barrier during HIV-1 infection, triggering neuronal dysfunction. HIV-infected macrophages secrete cathepsin B (CATB), and serum amyloid p component (SAPC), inducing neuronal apoptosis by an unknown mechanism. We...

HIV-associated neurocognitive disorders (HAND) are prevalent despite combined antiretroviral therapy, affecting nearly half of HIV-infected patients worldwide. During HIV infection of macrophages secretion of the lysosomal protein, cathepsin B, is increased. Secreted cathepsin B has been shown to induce neurotoxicity. Oxidative stress is increased...

Objective HIV-infected monocytes can infiltrate the blood brain barrier as differentiated macrophages to the central nervous system, becoming the primary source of viral and cellular neurotoxins. The final outcome is HIV-associated cognitive impairment (HACI), which remain prevalent today, possibly due to the longer life-span of the patients treate...

Proteomics analyses of macrophage secretome from HACI patients. (XLSX)

Statistics of relative intensities obtained by microwave & magnetic proteomics of macrophages from HACI patients. (DOCX)

Validation of L-Plastin in HIV seronegative controls. (A) L-Plastin was tested by western blot from MDM lysates from HIV-seronegative controls (n = 4) and patients with HACI. (B) Densitometry analyses for the western blots were normalized against GAPDH. The statistical analysis between the three groups of patients was performed using One-way ANOVA...

Raw data of proteins identified by microwave & Magnetic Proteomics of macrophages from HACI patients. (XLSX)

The abuse of anabolic androgenic steroids (AAS) has been considered a major public health problem during decades. Supraphysiological doses of AAS may lead to a variety of neuroendocrine problems. Precisely, the hypothalamic-pituitary-gonadal (HPG) axis is one of the body systems that is mainly influenced by steroidal hormones. Fluctuations of the h...

Western blot membranes and antibodies information for (A) GSTM1, (B) GP3/GAPDH, (C) ERH, (D) PEBP1, (E) PDIA6/ERP. Each antibody is normalized to β-actin (right panels). (PDF)

Western blot membranes and antibodies information for (A) AR, (B) ER, (C) GnRH, (D) p-ERK, (E) p-P38. Each antibody is normalized to β-actin (right panels). (PDF)

Cystatin B is a cysteine protease inhibitor that induces HIV replication in monocyte-derived macrophages (MDM). This protein interacts with signal transducer and activator of transcription (STAT-1) factor and inhibits the interferon (IFN-β) response in Vero cells by preventing STAT-1 translocation to the nucleus. Cystatin B also decreases the level...

Antiretroviral therapy partially restores the immune system and markedly increases life expectancy of HIV-infected patients. However, antiretroviral therapy does not restore full health. These patients suffer from poorly understood chronic inflammation that causes a number of AIDS and non-AIDS complications. Here we show that chronic inflammation i...

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...

Drug abuse is a major risk factor in the development and progression of HIV-1. This study defines the alterations in the plasma proteome of HIV-1 infected women that use cocaine. Plasma samples from 12 HIV-seropositive Hispanic women under antiretroviral therapy were selected for this study. Six sample pairs were matched between non-drug users and...

Thirty to fifty per cent of HIV patients develop HIV associated neurocognitive disorders (HAND) despite combined antiretroviral therapy. HIV-1 infected macrophages release viral and cellular proteins that induce neuronal degeneration and death. We hypothesize that changes in the macrophage secretome of HIV-1 seropositive patients with HAND may diss...

HIV-1 infection of macrophages increases cathepsin B secretion and induces neuronal apoptosis, but the molecular mechanism remains unclear. We identified macrophage-secreted cathepsin B protein interactions extracellularly and their contribution to neuronal death in vitro. Cathepsin B was immunoprecipitated from monocyte-derived macrophage supernat...

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...

HIV-1-infected mononuclear phagocytes release soluble factors that affect the homeostasis in tissue. HIV-1 can prompt metabolic encephalopathy with the addition of neuronal dysfunction and apoptosis. Recently, we reported that HIV-1 enhances the expression and secretion of bioactive cathepsin B in monocyte-derived macrophages, ultimately contributi...

Substance abuse is a risk factor for HIV infection and progression to AIDS. Recent evidence establishes that cocaine use promotes brain perivascular macrophage infiltration and microglia activation. The lysosomal protease cathepsin B is increased in monocytes from patients with HIV dementia and its secretion induces 10-15 % of neurotoxicity. Here w...

Mononuclear phagocytes including monocytes and macrophages, are important defense components of innate immunity, but can be detrimental in HIV-1 infection by serving as the principal reservoirs of virus in brain and triggering a strong immune response. These viral reservoirs represent a challenge to HIV-1 eradication since they continue producing v...

Inequities in the incidence of HIV infection and AIDS with continued persistence of HIV-associated neurocognitive disorders (HAND) exist in populations in Hawaii (HI) and Puerto Rico (PR). We previously reported that peripheral monocyte HIV DNA levels are high in patients in Hawaii with HAND and we now hypothesize that similar findings would be obs...

: HIV-1-associated neurocognitive disorders (HAND) is triggered by immune activation of brain cells and remain prevalent during progressive viral infection despite antiretroviral therapy. Cathepsins and cystatins are lysosomal proteins secreted by macrophages and microglia, and may play important roles in neuroregulatory responses. Our laboratory h...

Chronic HIV infection leads to the development of cognitive impairments, designated as HIV-associated neurocognitive disorders (HAND). The secretion of soluble neurotoxic factors by HIV-infected macrophages plays a central role in the neuronal dysfunction and cell death associated with HAND. One potentially neurotoxic protein secreted by HIV-1 infe...

Cystatin B and signal transducer and activator of transcription-1 (STAT-1) phosphorylation have recently been shown to increase human immunodeficiency virus-1 (HIV-1) replication in monocyte-derived macrophages (MDM), but the molecular pathways by which they do are unknown. We hypothesized that cystatin B inhibits the interferon (IFN) response and...

Mononuclear phagocytes (monocytes, macrophages, and microglia) play an important role in innate immunity against pathogens including HIV. These cells are also important viral reservoirs in the central nervous system and secrete inflammatory mediators and toxins that affect the tissue environment and function of surrounding cells. In the era of anti...

Monocyte ingress into the brain during progressive human immunodeficiency virus (HIV-1) infection parallels the severity of cognitive impairments. Although activated monocyte phenotypes emerge in disease, the functional correlates of these cells remain unresolved. To this end, we studied the proteome of blood-derived monocytes obtained from Hispani...

The extinction of conditioned fear memories requires plasticity in the infralimbic medial prefrontal cortex (IL mPFC), but little is known about the molecular mechanisms involved. Brain-derived neurotrophic factor (BDNF) is a key mediator of synaptic plasticity in multiple brain areas. In rats subjected to auditory fear conditioning, BDNF infused i...

HIV-1 infection in placental macrophages is limited as evidence by low viral mRNA and protein production. HIV-infected PM show restricted replication as compared with MDM. We aimed to determine at what point in the viral replication cycle this restriction occurs in PM as compared with MDM. We performed Alu-LTR PCR for proviral DNA to detect differe...

Cystatin (CSTB, also known as stefin B), a cysteine protease inhibitor, recently was found to be down-regulated in the proteome of uninfected and HIV-1-infected placental macrophages (PMs) and associated with restricted HIV-1 replication in PM but not in monocyte-derived macrophages (MDMs). We investigated CSTB interactions with signal transducer a...

It is well documented that placental macrophages show lower levels of HIV-1 infection than monocyte-derived macrophages (MDM). We used proteomic methods to test the hypothesis that placental macrophages secrete different proteins as compared to MDM that may contribute to decreased HIV-1 replication. Placental macrophages and MDM were cultured for 1...

HIV-associated cognitive neurological disorders (HAND) prevail in the antiretroviral therapy era. Proteomics analysis of CSF revealed expression of Cu/Zn superoxide dismutase (Cu/Zn SOD) in Hispanic women with cognitive impairment (CI). We tested the hypothesis that there is reduced capacity of antioxidant enzymes in CI by measures of expression an...

The signature for human immunodeficiency virus type 1 (HIV-1) neurovirulence remains a subject of intense debate. Macrophage viral tropism is one prerequisite but others, including virus-induced alterations in innate and adaptive immunity, remain under investigation. HIV-1-infected mononuclear phagocytes (MPs; perivascular macrophages and microglia...

Cognitive impairment remains a major complication of advanced human immunodeficiency virus (HIV) infection despite the widespread use of anti-retroviral therapy. Diagnosis is made by exclusion making biomarkers of great potential use. Thus, we used an integrated proteomics platform to assess cerebrospinal fluid protein profiles from 50 HIV-1 seropo...

Mononuclear phagocytes (MP; monocytes, tissue macrophages, and dendritic cells) are reservoirs, vehicles of dissemination, and targets for persistent HIV infection. However, not all MP population equally support viral growth. Such differential replication is typified by the greater ability of placental macrophages (PM), as compared to blood borne m...

HIV infection is increasing in minority groups, particularly in African American and Hispanic women. Although the incidence of HIV dementia has decreased since the advent of highly active antiretroviral treatment, prevalence of neurocognitive complications has increased as patients are now living longer. This study's purpose was to determine the ps...

Cigarette smoking alters the immune system and may improve cognitive deficits in neuropsychiatric disorders. Smoking prevalence is high in human immunodeficiency virus (HIV)-infected patients; however, its effect on HIV-associated cognitive impairment remains unknown in the era of antiretroviral treatment. The authors examined associations of smoki...

Advanced HIV-1 infection is commonly associated with progressive immune suppression and the development of cognitive, motor, and behavior disturbances. In its most severe form, it is diagnosed as HIV-1 associated dementia (HAD) and can progress to profound functional disability and death. Despite prodigious efforts to uncover biomarkers of HAD, non...

Human immunodeficiency virus type 1 (HIV-1) tropism plays an important role in HIV-associated dementia. In this study, aimed at determining if the tropism and coreceptor usage of circulating viruses correlates with cognitive function, the authors isolated and characterized HIV from the peripheral blood of 21 Hispanic women using antiretroviral ther...

Human immunodeficiency virus (HIV)-associated cognitive impairment, a significant cause of morbidity, affects up to 30% of HIV-infected people. Its prevalence doubled as patients began to live longer after the introduction of highly active retroviral therapy. Women are now one of the fastest growing groups with acquired immunodeficiency syndrome (A...

Hispanic women represent one of the fastest growing groups with HIV infection in the United S. In Puerto Rico 27.4% of the reported cases of HIV/AIDS are women (1996-2004). Research focusing specially on women living with HIV is now gaining scientific attention since it has been clearly established that there are important biological, psychological...

Infection of the central nervous system (CNS) by the human immunodeficiency virus (HIV) causes a broad spectrum of behavioral, motor, and cognitive dysfunctions. In its most severe form, HIV-1-associated dementia or HAD, occurs late in viral infection, often associated with profound immunosuppression. Disease is perpetuated by cellular and viral ne...