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Current Opinion in Virology Feb 2014Human Immunodeficiency Virus (HIV) initiates infection by fusing its envelope membrane with the cell membrane through a process which is triggered through interactions... (Review)
Review
Human Immunodeficiency Virus (HIV) initiates infection by fusing its envelope membrane with the cell membrane through a process which is triggered through interactions with the cellular receptor and coreceptor. Although the mechanism of HIV fusion has been extensively studied, the point of its entry into cells remains controversial. HIV has long been thought to fuse directly with the cell plasma membrane. However, several lines of evidence suggest that endocytic entry of HIV can lead to infection and, moreover, that endocytosis could be the predominant HIV entry pathway into different cell types. This review discusses recent findings pertinent to HIV entry routes and novel approaches to pinpoint the sites of virus entry.
Topics: HIV; Host-Pathogen Interactions; Humans; Virus Internalization
PubMed: 24525288
DOI: 10.1016/j.coviro.2013.09.004 -
Clinical and Vaccine Immunology : CVI Apr 2016A concern during the early AIDS epidemic was the lack of a test to identify individuals who carried the virus. The first HIV antibody test, developed in 1985, was... (Review)
Review
A concern during the early AIDS epidemic was the lack of a test to identify individuals who carried the virus. The first HIV antibody test, developed in 1985, was designed to screen blood products, not to diagnose AIDS. The first-generation assays detected IgG antibody and became positive 6 to 12 weeks postinfection. False-positive results occurred; thus, a two-test algorithm was developed using a Western blot or immunofluorescence test as a confirmatory procedure. The second-generation HIV test added recombinant antigens, and the third-generation HIV tests included IgM detection, reducing the test-negative window to approximately 3 weeks postinfection. Fourth- and fifth-generation HIV assays added p24 antigen detection to the screening assay, reducing the test-negative window to 11 to 14 days. A new algorithm addressed the fourth-generation assay's ability to detect both antibody and antigen and yet not differentiate between them. The fifth-generation HIV assay provides separate antigen and antibody results and will require yet another algorithm. HIV infection may now be detected approximately 2 weeks postexposure, with a reduced number of false-positive results.
Topics: Diagnostic Tests, Routine; HIV; HIV Infections; Humans; Immunoassay
PubMed: 26936099
DOI: 10.1128/CVI.00053-16 -
Current Opinion in Structural Biology Apr 2015Antiviral restriction factors are an integral part of the host innate immune system that protects cells from viral pathogens, such as human immunodeficiency virus (HIV).... (Review)
Review
Antiviral restriction factors are an integral part of the host innate immune system that protects cells from viral pathogens, such as human immunodeficiency virus (HIV). Studies of the interactions between restriction factors and HIV have greatly advanced our understanding of both the viral life cycle and basic cell biology, as well as provided new opportunities for therapeutic intervention of viral infection. Here we review the recent developments towards establishing the structural and biochemical bases of HIV inhibition by, and viral countermeasures of, the restriction factors TRIM5, MxB, APOBEC3, SAMHD1, and BST2/tetherin.
Topics: Animals; DNA, Viral; HIV; Humans; Immune Evasion; Mutation; Reverse Transcription
PubMed: 25939065
DOI: 10.1016/j.sbi.2015.04.004 -
The Journal of Infectious Diseases Mar 2017Current HIV therapy is not curative regardless of how soon after infection it is initiated or how long it is administered, and therapy interruption almost invariably... (Review)
Review
Current HIV therapy is not curative regardless of how soon after infection it is initiated or how long it is administered, and therapy interruption almost invariably results in robust viral rebound. Human immunodeficiency virus persistence is therefore the major obstacle to a cure for AIDS. The testing and implementation of novel yet unproven approaches to HIV eradication that could compromise the health status of HIV-infected individuals might not be ethically warranted. Therefore, adequate in vitro and in vivo evidence of efficacy is needed to facilitate the clinical implementation of promising strategies for an HIV cure. Animal models of HIV infection have a strong and well-documented history of bridging the gap between laboratory discoveries and eventual clinical implementation. More recently, animal models have been developed and implemented for the in vivo evaluation of novel HIV cure strategies. In this article, we review the recent progress in this rapidly moving area of research, focusing on the two most promising model systems: humanized mice and nonhuman primates.
Topics: Animals; Anti-HIV Agents; Disease Models, Animal; HIV; HIV Infections; Humans; Primates; Virus Latency
PubMed: 28520967
DOI: 10.1093/infdis/jiw637 -
The Journal of Infectious Diseases Mar 2017Quiescent proviral genomes that persist during human immunodeficiency virus type 1 (HIV-1) infection despite effective antiretroviral therapy (ART) can fuel rebound... (Review)
Review
Quiescent proviral genomes that persist during human immunodeficiency virus type 1 (HIV-1) infection despite effective antiretroviral therapy (ART) can fuel rebound viremia after ART interruption and is a central obstacle to the cure of HIV infection. The induction of quiescent provirus is the goal of a new class of potential therapeutics, latency reversing agents (LRAs). The discovery, development, and testing of HIV LRAs is a key part of current efforts to develop latency reversal and viral clearance strategies to eradicate established HIV infection. The development of LRAs is burdened by many uncertainties that make drug discovery difficult. The biology of HIV latency is complex and incompletely understood. Potential targets for LRAs are host factors, and the potential toxicities of host-directed therapies in individuals that are otherwise clinically stable may be unacceptable. Assays to measure latency reversal and assess the effectiveness of potential therapeutics are complex and incompletely validated. Despite these obstacles, novel LRAs are under development and beginning to enter combination testing with viral clearance strategies. It is hoped that the steady advances in the development of LRAs now being paired with emerging immunotherapeutics to clear persistently infected cells will soon allow measurable clinical advances toward an HIV cure.
Topics: Anti-HIV Agents; HIV; HIV Infections; Humans; Proviruses; Virus Activation; Virus Latency
PubMed: 28520964
DOI: 10.1093/infdis/jiw618 -
The Yale Journal of Biology and Medicine 1987In just six years after the initial description of the acquired immunodeficiency syndrome, much has been learned about the etiologic agent, the human immunodeficiency... (Review)
Review
In just six years after the initial description of the acquired immunodeficiency syndrome, much has been learned about the etiologic agent, the human immunodeficiency virus. The pathogenic mechanisms utilized by this virus to infect selectively and persistently T4+ lymphocytes and monocyte/macrophages, leading to immunodeficiency and neurologic dysfunction, are slowly becoming clear. Better understanding of the pathogenesis of human immunodeficiency virus infection is essential for the rational design of therapeutic and preventive strategies to combat this deadly virus.
Topics: Acquired Immunodeficiency Syndrome; Antiviral Agents; HIV; Humans; Macrophages; Monocytes; T-Lymphocytes; Viral Vaccines; Virus Replication
PubMed: 3324508
DOI: No ID Found -
FEBS Letters Jul 2016The recent development of fluorescence microscopy approaches overcoming the diffraction limit of light microscopy opened possibilities for studying small-scale cellular... (Review)
Review
The recent development of fluorescence microscopy approaches overcoming the diffraction limit of light microscopy opened possibilities for studying small-scale cellular processes. The spatial resolution achieved by these novel techniques, together with the possibility to perform live-cell and multicolor imaging, make them ideally suited for visualization of native viruses and subviral structures within the complex environment of a host cell or organ, thus providing fundamentally new possibilities for investigating virus-cell interactions. Here, we review the use of super-resolution microscopy approaches to study virus-cell interactions, and discuss recent insights into human immunodeficiency virus biology obtained by exploiting these novel techniques.
Topics: HIV; Humans; Imaging, Three-Dimensional; Microscopy, Fluorescence; Virus Replication
PubMed: 27117435
DOI: 10.1002/1873-3468.12186 -
Wiley Interdisciplinary Reviews. RNA 2015MicroRNAs (miRNAs) and long-noncoding RNAs (lncRNAs) are involved in many biological processes, including viral replication. In this review, the role of miRNAs and... (Review)
Review
MicroRNAs (miRNAs) and long-noncoding RNAs (lncRNAs) are involved in many biological processes, including viral replication. In this review, the role of miRNAs and lncRNAs in human immunodeficiency virus (HIV) replication will be discussed. The review focuses on miRNAs that target cellular proteins involved in HIV replication-proteins that mediate steps in the viral life cycle, as well as proteins of the innate immune system that inhibit HIV replication. Given the large number of miRNAs encoded in the human genome, as well as the large number of cellular proteins involved in HIV replication, the number of miRNAs identified to date that affect viral replication are certainly only the 'tip of the iceberg'. The review also discusses two lncRNAs that are involved in HIV gene regulation-7SK RNA and NEAT1 RNA. 7SK RNA is involved in HIV Tat protein stimulation of RNA polymerase II elongation of the integrated provirus, while NEAT1 RNA is involved in HIV Rev protein export of incompletely spliced viral transcripts.
Topics: HIV; Humans; MicroRNAs; RNA, Long Noncoding; Virus Replication
PubMed: 26394053
DOI: 10.1002/wrna.1308 -
The Journal of General Virology Jan 2013The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) pandemic is amongst the most important current worldwide public health threats.... (Review)
Review
The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) pandemic is amongst the most important current worldwide public health threats. While much research has been focused on AIDS vaccines that target the surface viral envelope (Env) protein, including gp120 and the gp41 ectodomain, the C-terminal tail (CTT) of gp41 has received relatively little attention. Despite early studies highlighting the immunogenicity of a particular CTT sequence, the CTT has been classically portrayed as a type I membrane protein limited to functioning in Env trafficking and virion incorporation. Recent studies demonstrate, however, that the Env CTT has other important functions. The CTT has been shown to additionally modulate Env ectodomain structure on the cell and virion surface, affect Env reactivity and viral sensitivity to conformation-dependent neutralizing antibodies, and alter cell-cell and virus-cell fusogenicity of Env. This review provides an overview of the Env structure and function with a particular emphasis on the CTT and recent studies that highlight its functionally rich nature.
Topics: Animals; HIV; HIV Envelope Protein gp41; Humans; Structure-Activity Relationship; Viral Envelope Proteins
PubMed: 23079381
DOI: 10.1099/vir.0.046508-0 -
Journal of Virology Sep 2016The cells that are targeted by primate lentiviruses (HIV and simian immunodeficiency virus [SIV]) are of intense interest given the renewed effort to identify potential... (Review)
Review
The cells that are targeted by primate lentiviruses (HIV and simian immunodeficiency virus [SIV]) are of intense interest given the renewed effort to identify potential cures for HIV. These viruses have been reported to infect multiple cell lineages of hematopoietic origin, including all phenotypic and functional CD4 T cell subsets. The two most commonly reported cell types that become infected in vivo are memory CD4 T cells and tissue-resident macrophages. Though viral infection of CD4 T cells is routinely detected in both HIV-infected humans and SIV-infected Asian macaques, significant viral infection of macrophages is only routinely observed in animal models wherein CD4 T cells are almost entirely depleted. Here we review the roles of macrophages in lentiviral disease progression, the evidence that macrophages support viral replication in vivo, the animal models where macrophage-mediated replication of SIV is thought to occur, how the virus can interact with macrophages in vivo, pathologies thought to be attributed to viral replication within macrophages, how viral replication in macrophages might contribute to the asymptomatic phase of HIV/SIV infection, and whether macrophages represent a long-lived reservoir for the virus.
Topics: Acquired Immunodeficiency Syndrome; Animals; Disease Reservoirs; HIV; Humans; Macrophages; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Virus Replication
PubMed: 27307568
DOI: 10.1128/JVI.00672-16