Results
An HIV GWAS SNP marks expression of a long non-coding RNA (lncRNA).
Human chromosome 3p21–22 harbors a cluster of chemokine receptor genes, several of which serve as major or minor co-receptors of HIV-1 [1]. The genetic associations of CCR5 and CCR2 gene polymorphisms with HIV-1 pathogenesis are well known [2-5], but any potential role of variation in other regions of the cluster is largely unknown. An intergenic SNP (rs1015164 A/G) downstream of the CCRL2 gene was shown to associate with HIV viral load control [6] and progression to AIDS [7] in two independent cohorts of HIV-infected patients. Importantly, the SNP showed genome-wide significant association with HIV outcomes in meta-analyses that collectively examined genotyping data from 6,315 HIV-infected patients [8]. The SNP is in close genomic proximity to a non-coding RNA gene RP-11-24F11.2 (Fig. S1). We were able to detect and quantify the polyadenylated lncRNA transcript in the total RNA from peripheral blood lymphocytes (PBLs) using quantitative PCR (qPCR). Specificity of the primers was confirmed by sequencing of the amplicons. We designated this lncRNA as Lnc11.2. The rs1015164A allele, which associated with higher viral loads (OR=1.4, p=3.3 ×10-5) [6] and more rapid disease progression (HR=1.4, p=8.6 ×10-6) [7] correlated with higher expression levels of Lnc11.2 in PBLs (Fig. 1).
Characterization of the Lnc11.2 transcript Amplification of the 3’and 5’ends of the Lnc11.2 transcript uncovered the
The CCR5 gene codes for a protein found on the surface of white blood cells that acts as a receptor for chemokines. The HIV virus, strain R5-tropic virus, initially uses the CCR5 chemokine receptor to attach to the CD4+ helper T-cells. The Berlin patient showed how a CCR5-negative hematopoietic stem/ progenitor cells (HSC) from a CCR5 ∆ 32 donor can be used to generate HIV-1 resistant CD4+ helper T-cells.3 Mice models using in vivo studies have also shown ZFNs to be very effective in creating this CCR5 ∆ 32 mutation and ultimately suppressing the HIV-1 replication. Holt and collegues3 performed a study using a mice model to demonstrate the use of ZFN-modified autologous HSC as a clinical approach to treat
This study shows that 6% of the entire annotated non-coding and coding gene transcripts are overlapping with small RNAs. Highly specific subcellular positioning is found for both unannotated & annotated short RNA.
directly influences the risk for or course of HIV-1 infection or is a marker for other exposurerelated
The Center for Disease Control provides leadership, guidance, and research to help control the Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) epidemic by working alongside the communities on a state and national level. They are also partners with other countries abroad in research, surveillance and evaluation of activities among the world’s population. The activities monitored are critical to CDC due to the estimated 1.1 million Americans infected with the disease. Some of these infected populations do not know they are infected and the number increases each year.
The most fundamental question to ask about an HIV vaccine is: 'What evidence exists that protection against disease after exposure to HIV is possible?' The best evidence for successful protection against a virulent primate lentivirus such as HIV is that monkeys are almost always protected against challenge with pathogenic SiVmac after vaccination with an attenuated (ne/-deleted) SIVmac
When MYCN was successfully fully cloned into cDNA, the transcript was found to encode 456 amino acids and the molecular weight of this product was determined to be 49 kD, the same weight as MYC (Stanton et al, 1986). The newly cloned MYCN was also found to have a high degree of similarity at the C terminus between both MYC and MYCN (Stanton et al, 1986). MYC was known to be a transcription factor that binds to enhancer sequences to activate gene transcription for promoting proliferation and cell cycle progression (Gallant, 2013). Due to the high degree of similarity at the DNA binding domain of both proteins, it suggested that both products possible bind to the same enhancer. A high degree of similarity between the 5’ and 3’ UTRs also suggested both transcripts are regulated in the same manner (Stanton et al, 1986). Besides a high degree of similarity, it has been found that both MYCN and MYC have a basic helix-loop-helix/leucine zipper conformation, and that both transcription factors heterodimerize with another protein MAX to bind to certain enhancer sequences to stimulate transcription (Stanton et al,
Recently in Cuba a new and aggressive strain of HIV has been discovered and this strain causes an early development of AIDS in people within 3 years of being infected with HIV. Usually it takes five to ten years for a person with HIV to progress to AIDS but only if the person is not under anti-retroviral therapy treatment. Individuals who are HIV positive usually don’t feel or look sick immediately which is why they do not take ART treatment during the clinical latency stage of the infection. The new “recombinant” strain of HIV takes advantage of this situation by causing a rapid progression of HIV to AIDS and cutting short the time needed for HIV positive patients to exhibit early symptoms, which could help them be aware of their infection
The HIV-1 life cycle is complicated and its period and result is contingent upon the target cell type and cell activation. In the beginning, HIV-1 enters the cells without producing instant damage but by entering the cells it can provoke intracellular signal cascades, which may assist the progress of viral replication. The external glycoprotein (gp120) and the transmembrane protein (gp141) are two molecules on the HIV-1 envelope that form the spikes on the virion’s surface. In the entry process, gp120 first attaches to the CD4+ receptor and then attaches to the cell membrane. Interactions between the virus and chemokine co-receptors will cause permanent conformational changes. The fusion event will occur within minutes by pore formation and it will discharge the viral core into the cell cytoplasm. Once the core dismantles, the viral genome will be reverse transcribed into DNA by the virus’ own reverse transcriptase enzyme. Viral variants may develop at the time of this process because reverse transcriptase is error prone. During the midpoint of infection, both the viral protein integrase and the host DNA repair enzymes will inject the viral genome into the active domain of the host’s chromosomal DNA. Lens epithelium-derived growth factor (LEDGF/p75) is an integrase binding host factor that assists the progress of integration, which converts the cell into a virus producer. In the late stages, production of viral particles will need both host driven and virus driven
Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is a global epidemic: 25 million people have died from it and 35 million people are currently infected1. While anti-retroviral therapies are available that control viral replication, those treatments are unable to purge the latent reservoir of virus resident in resting CD4+ memory T cells. Additionally, these treatments are extremely expensive and largely unavailable to those in developing countries where 90% of infected individuals reside1. Therefore, the best approach for controlling and preventing the transmission of HIV would be a prophylactic vaccine.
Our chosen article is titled “HIV and AIDS News and Updates: New Strain of HIV Found in Cuba Which Can Develop Into a Full-Blown AIDS in a Span of Only 3 Years” written by Steff Lyn Smetham. It was published on November 5th, 2015 on the Crossmap online website. The article was written to inform the readers on a newly discovered strain of HIV, which develops faster than the average known types of HIV. This article mentioned many recently studied concepts including, the rate of disease progression, CRF19’s involvement in the AID’s rapid progression (AID’s-RP), the adverse effects of RANTES defense molecules, and proper HIV treatment. The general consensus is that the average rate of disease progression takes approximately 5 to 10 years to progress into AIDS, however, it is quite complicated to pinpoint the rate due to many factors. Based on many clinical studies done with a diverse group of patients in Cuba, CRF19 has shown to be one of the main recombinant subtype responsible for AIDs-RP. In addition, CCL5 and CCL2 of the RANTES family, have proven to be two specific chemokines that display the adverse effects . Finally, regardless of CD4+ count, treatment should be started immediately preferably with the common therapies Isoniazid preventive therapy (IPT) and Co-trimoxazole preventive therapy (CPT). The authors have used information through studies being done at the University of Leuven located in Belgium, and Professor Anne-Mieke Vandamme and a team
Human Immunodeficiency Virus (HIV), the agent causing AIDS, is arguably the deadliest infectious disease to affect humans. Not only because of the affects it has on the body by the eventual collapse of the immune system, but because it is a master at evading and escaping the immune responses and antiretroviral drugs by constantly mutating and maintaining genetic variation. Vaccines are designed to recognize specific viral antigens which makes it almost impossible to develop one against HIV. Recent studies have claimed that it is the immune response that puts the selective pressure on the virus to mutate that allows it to escape and persist. Others claim that it is the large turn over rate, rapid mutation rate, or ability to hide latently integrated into the host cell’s DNA. Here I will present specific studies to try to determine what is the dominating factor that allows HIV to escape and persist.
To investigate the distribution of PI-induced mutational changes in HIV-1 across Gag and protease regions, Codoner et al. sequenced the HIV-1 Gag-protease coding region from longitudinal plasma samples from four patients receiving PI treatment over a 9-year period. Sequence analysis confirmed that HIV-1, in response to PIs, demonstrates a stepwise accumulation of Gag cleavage site mutations (CSM) at the following positions: V128I in the p17/p24 junction; S373P and I376V at the p2/NC junction; A431V at the NC/p1 junction; K436R at the NC/p1 junction and P453A at the p1/p6 junction (Codoner et al, 2017). Of these Gag CSM, A431V and K436R have been previously associated with drug resistance mutations in the protease and V128I, A431V, K436R
Late (165). These multifunctional proteins are coded by five different transcripts that are formed in
There has been countless number of efforts to develop an effective gene transfer approach to treat HIV-1 infections globally. Many transgenes have been identified to inhibit in vitro HIV-1 infections. As drug resistant HIV-1 is increasingly common even with patients receiving HAART, designing drug treatment methods have been challenging. Therefore, investigation into new therapeutic approaches should continue. Gene delivery plays an important supporting role developing potential therapies directed towards HIV-1 infections. The goals of the anti-HIV-1 gene therapy are to deliver transgenes to directly susceptible cells, Immunize against HIV-1 antigens, inhibit HIV-1 proliferation in target organs, and deliver to Hematopoietic Progenitor Cells. Delivering transgenes to susceptible cells will make them resistant to HIV-1 infections and inhibit viral replication. When CCR5 a major coreceptor for HIV was disrupted in the “Berlin Patient” led to the revival of gene therapy. The naturally occurring CCR5-Δ32 mutation that results in a frameshift mutation dislocates the CCR5 expression on the cell surface. The “Berlin patient” who was HIV+ patient with lymphoma was transplanted with bone marrow from a donor with CCR5-Δ32 mutation and became ‘cured’ of HIV. But as only a small general population with CCR5-Δ32 mutation can be identified alternative methods must be identified for gene therapy.
Prevention and protection is the most cost effective method to reduce the spread of HIV. In mid-1990s Cambodia's prevention efforts have centered generally on encouraging the condom use among men when participating in business sex and swaying men to diminish their business sex activity. In 1999, the Cambodian government launched a 100% condom usage campaign among the brothel sex workers that was modeled from Thailand's successful program.