TZA, a Sensitive Reporter Cell-based Assay to Accurately and Rapidly Quantify Inducible, Replication-competent Latent HIV-1 from Resting CD4 T Cells.

The latent HIV-1 viral reservoir in resting CD4 (rCD4) T cells represents a major barrier to an HIV-1 cure. There is an ongoing effort to identify therapeutic approaches that will eliminate or reduce the size of this reservoir. However, clinical investigators lack an assay to determine whether or not a decrease in the latent reservoir has been achieved.

Type 1-programmed dendritic cells drive antigen-specific latency reversal and immune elimination of persistent HIV-1.

Background: Despite the success of antiretroviral therapy (ART), latent HIV-1 continues to persist in a long-lived population of resting memory CD4 T cells within those who are infected. Finding a safe and effective means to induce latency reversal (LR) during ART to specifically expose this latent HIV-1 cellular reservoir for immune elimination has been a major barrier to a functional cure.

Methods: In this study, we test the use of antigen-presenting type 1-polarized, monocyte-derived dendritic cells (MDC1) generated from chronic HIV-1-infected individuals on ART as a means to induce HIV-1 latency reversal in autologous CD4 T cells harboring replication-competent provirus.

Neisseria gonorrhoeae uses cellular proteins CXCL10 and IL8 to enhance HIV-1 transmission across cervical mucosa.

Problem: Neisseria gonorrhoeae (NG) infection has been shown to increase sexual transmission of HIV-1. However, the mechanism of NG-induced enhanced HIV-1 transmission is unknown.

Methods: (a) The cervical tissues were exposed to NG, and cytokine induction was monitored by measuring cytokine proteins in culture supernatants and cytokine mRNAs in tissues.

Inhibitors of Signaling Pathways That Block Reversal of HIV-1 Latency.

Signaling pathways play a key role in HIV-1 latency. In this study, we used the 24ST1NLESG cell line of HIV-1 latency to screen a library of structurally diverse, medicinally active, cell permeable kinase inhibitors, which target a wide range of signaling pathways, to identify inhibitors of HIV-1 latency reversal. The screen was carried out in the absence or presence of three mechanistically distinct latency-reversing agents (LRAs), namely, prostratin, panobinostat, and JQ-1.

Human immunodeficiency virus infection induces lymphoid fibrosis in the BM-liver-thymus-spleen humanized mouse model.

A major pathogenic feature associated with HIV infection is lymphoid fibrosis, which persists during antiretroviral therapy (ART). Lymphoid tissues play critical roles in the generation of antigen-specific immune response, and fibrosis disrupts the stromal network of lymphoid tissues, resulting in impaired immune cell trafficking and function, as well as immunodeficiency. Developing an animal model for investigating the impact of HIV infection-induced lymphoid tissue fibrosis on immunodeficiency and immune cell impairment is critical for therapeutics development and clinical translation.

Preformulation and Vaginal Film Formulation Development of Microbicide Drug Candidate CSIC for HIV prevention.

Purpose: 5-chloro-3-[phenylsulfonyl] indole-2-carboxamide (CSIC) is a highly potent non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1 which has been shown to have a more desirable resistance profile than other NNRTIs in development as HIV prevention strategies. This work involves generation of preformulation data for CSIC and systematic development of a cosolvent system to effectively solubilize this hydrophobic drug candidate. This system was then applied to produce a polymeric thin film solid dosage form for vaginal administration of CSIC for use in prevention of sexual acquisition of HIV.

Novel assay reveals a large, inducible, replication-competent HIV-1 reservoir in resting CD4 T cells.

Although antiretroviral therapy can suppress HIV-1 infection to undetectable levels of plasma viremia, integrated latent HIV-1 genomes that encode replication-competent virus persist in resting CD4 T cells. This latent HIV-1 reservoir represents a major barrier to a cure. Currently, there are substantial efforts to identify therapeutic approaches that will eliminate or reduce the size of this latent HIV-1 reservoir.

Effect of prolonged freezing of semen on exosome recovery and biologic activity.

Exosomes are important vehicles of intercellular communication that shape host responses to physiologic, tumorigenic, and pathogenic conditions. The composition and function of exosomes are dynamic and depends on the state and condition of the cellular source. In prior work, we found that semen exosomes (SE) from healthy donors who do not use illicit drugs potently inhibit HIV-1.

Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV.

Background: Infection with human immunodeficiency virus (HIV) influences the outcome and natural disease progression of hepatitis C virus (HCV) infection. While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop chronic HCV infection, 20-46% of mono- and co-infected subjects spontaneously clear HCV infection. The mechanism underlying viral clearance is not clearly understood.

Placental Mechanics in the Zika-Microcephaly Relationship.

How the Zika virus (ZIKV) accesses the embryo remains unknown. In this issue, Quicke et al. (2016) use an in vitro model of the human placenta to show that placental macrophages are more permissive to ZIKV infection than trophoblasts, which may be refractory to infection (Bayer et al.

Effective Cytotoxic T Lymphocyte Targeting of Persistent HIV-1 during Antiretroviral Therapy Requires Priming of Naive CD8+ T Cells.

Unlabelled: Curing HIV-1 infection will require elimination of persistent cellular reservoirs that harbor latent virus in the face of combination antiretroviral therapy (cART). Proposed immunotherapeutic strategies to cure HIV-1 infection include enhancing lysis of these infected cells by cytotoxic T lymphocytes (CTL). A major challenge in this strategy is overcoming viral immune escape variants that have evaded host immune control.

HIV Exposure to the Epithelia in Ectocervical and Colon Tissues Induces Inflammatory Cytokines Without Tight Junction Disruption.

Epithelial cells in human cervical and colonic mucosa do not express HIV receptor. However, HIV transmission occurs across the unbreached epithelia by an unknown mechanism. In this study, the effect of HIV exposure on tight junction (TJ) and cytokine production in ectocervical and colon mucosal epithelia in tissue biopsies was investigated in an organ culture model.

Acute complications following intracavitary high-dose-rate brachytherapy in uterine cancer.

Purpose: Almost 30% of malignancies in women of developing countries are gynecological and brachytherapy is an integral part of management of these patients. Reports of complications (both acute and late) of high-dose-rate (HDR) intracavitary brachytherapy are sparse in world literature due to relatively small number of gynecological malignancies, particularly in advanced stage, in developed countries. High-dose-rate brachytherapy is gaining popularity in developing countries due to scientific and economic reasons.

Abasic phosphorothioate oligomers inhibit HIV-1 reverse transcription and block virus transmission across polarized ectocervical organ cultures.

In the absence of universally available antiretroviral (ARV) drugs or a vaccine against HIV-1, microbicides may offer the most immediate hope for controlling the AIDS pandemic. The most advanced and clinically effective microbicides are based on ARV agents that interfere with the earliest stages of HIV-1 replication. Our objective was to identify and characterize novel ARV-like inhibitors, as well as demonstrate their efficacy at blocking HIV-1 transmission.

The CD8 antiviral factor (CAF) can suppress HIV-1 transcription from the long terminal repeat (LTR) promoter in the absence of elements upstream of the CATATAA box.

Background: The CD8 Antiviral Factor (CAF) suppresses viral transcription from the HIV-1 Long Terminal Repeat (LTR) promoter in a non-cytolytic manner. However, the region on the LTR upon which CAF acts is unknown. Our objective was to determine the region on the LTR upon which CAF acts to suppress HIV-1 transcription.

Bone metastasis.

Rectal cancers may rarely metastasize in bone and when it occurs, is usually preceded by lung and/or liver metastasis. However, whether it may ever bypasses other organs, particularly lung and liver and metastasizes directly to bone or not, is debatable. Some authors have described the presence of isolated bone metastasis from colo-rectal cancers, whereas others have questioned its' existence in the absence of lung or liver metastasis.

Dendritic cells restore CD8+ T cell reactivity to autologous HIV-1.

Unlabelled: Recall T cell responses to HIV-1 antigens are used as a surrogate for endogenous cellular immune responses generated during infection. Current methods of identifying antigen-specific T cell reactivity in HIV-1 infection use bulk peripheral blood mononuclear cells (PBMC) yet ignore professional antigen-presenting cells (APC) that could reveal otherwise hidden responses. In the present study, peptides representing autologous variants of major histocompatibility complex (MHC) class I-restricted epitopes from HIV-1 Gag and Env were used as antigens in gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) and polyfunctional cytokine assays.

Transmission and evolution of hepatitis C virus in HCV seroconverters in HIV infected subjects.

HIV/HCV co-infection provides a model to determine the role of immunity on HCV transmission and evolution. In this study HCV transmission and evolution were evaluated in 6 HCV seroconverters in HIV-infected subjects with a wide range of CD4 cell count. The HCV envelope E1/E2 sequences were analyzed for transmission bottleneck, viral diversity/divergence, immune pressure, and mutations of HLA class I/II restricted epitopes.

Adenoma malignum of the uterine cervix--an enigma.

Adenoma malignum is a rare variant of cervical adenocarcinoma which presents a great diagnostic and therapeutic challenge to an oncologist. A 31-year-old woman presented with a mass filling up whole of the vagina which showed no evidence of malignancy by scraping cytology or punch biopsy. But histological examination of the resected mass turned up to be adenoma malignum of the cervix.

Adrenal neuroblastoma in an adult.

Adrenal neuroblastomas, although quite common in children, are extremely rare in adulthood. Here, we are reporting the case of a 47-year-old male who presented with right flank pain and had a palpable mass in the same region. Contrast-enhanced computed tomography showed an irregular, poorly marginated heterogeneous mass lesion arising from the right suprarenal position.

A compensatory mutation provides resistance to disparate HIV fusion inhibitor peptides and enhances membrane fusion.

Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals.

A comparison of dose distribution from Manchester-style and Fletcher-style intracavitary brachytherapy applicator systems in cervical cancer.

Purpose: During intracavitary brachytherapy (ICBT) for cervical cancer, the choice of applicator system remains rather arbitrary. However, as the applicator geometry may play an important role in dose distribution, thereby improving the therapeutic ratio, this study was conducted to compare the Manchester-style and Fletcher-style applicator systems.

Material And Methods: After completion of EBRT, 22 patients with cervical cancer (stage IIA-IIIB) underwent intracavitary brachytherapy.