Host genes associated with HIV/AIDS: advances in gene discovery
Identification of genes that affect susceptibility and resistance to HIV-1 is key to .. A 32 base pair deletion (CCR5 Δ32) results in a truncated CCR5 protein that is . Most studies reported a positive correlation between expression levels and . Abstract. The relationship between virion protein maturation and genomic RNA dimerization of human immunodeficiency virus type 1 (HIV-1). HIV-1 has been found to require Vif to synthesize infectious viruses in lymphocytes, macrophages, and certain.
We have constructed HIV-1 Gag cleavage site mutants to enable the steady state observation of virion maturation steps, and precisely study Gag processing, RNA dimerization, virion morphology and infectivity.
However, the primary cleavage alone is not sufficient, and the ensuing cleavages are required for the completion of dimerization.
From our observations, the increase of cleavage products may not put a threshold on the transition from fragile to stable dimeric RNA.
Structure and genome of HIV - Wikipedia
Most of the RNA dimerization process did not require viral core formation, and particle morphology dynamics during viral maturation did not completely synchronize with the transition of dimeric RNA status. The viral genome always occurs as a dimer in virus particles, and the interaction is non-covalent since heating easily dissociates purified dimeric genomes into monomers. Genomic RNA dimerization is believed to be a crucial step for the life cycle of retroviruses.
Template strand switching between two genomes during reverse transcription is often observed in the retroviral lifecycle 1. It is likely that the presence of two genomes in one virion helps the virus survive by providing genetic variety for their progeny 2. However, this may not fully explain why the virion is required to carry two identical RNAs in spite of severe space limitation, since retroviruses with little sequence variety such as HTLV-1 3 are also dimeric.
Identification of cis-acting signals for retrovirus genome dimerization, called the dimer linkage structure DLSwas initially attempted in an in vitro assay 4—8. Although the DLS on viral RNA is suggested to be involved in dimer formation and its close relationship to the packaging signal has been studied 2there remains incompletely understood issues about the overall mechanisms and the precise nature of retroviral genome dimerization.
Maturation changes virion morphology from the immature particle, called donut-shaped particle, to the mature virion; a particle lined with viral matrix proteins containing a condensed core composed of a viral capsid shell caging ribonucleoprotein RNP complex, comprised of viral RNA, nucleocapsid and enzymes Maturation prepares the virus for infection of adjacent hosts and is inevitably essential for particle infectivity.
Although many aspects about how the process of virion maturation contributes to achieving infectivity remain unclear, it is a well-accepted idea that viral RNA within the virion forms a stable and uniform dimer only after complete virion maturation.
Structure and genome of HIV
Obviously, viral protease PR activity to process Gag precursor protein Pr55 is required for stable genomic RNA dimerization in the virion. It has been suggested that Gag precursor, as well as viral NC protein, have RNA chaperone activity and are required for the proper formation of dimeric RNA in the virion 11 Some preceding studies suggested that specific Gag cleavage sites or protein regions contribute to viral genome dimerization 16— In light of these findings, we constructed two sets of Gag mutants which could represent cleavage intermediates, effectively snapshooting the process of virion maturation in this study.
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To systematically clarify the dynamic correlation between viral RNA and protein maturation in viral life cycle, virion protein, genomic RNA, virion morphology and infectivity of these mutants were examined comprehensively.
Disease progression Figure 1: With a seroconverter i.HIV genomic structure and function
When the date of infection is unknown, KM survival and Cox models are not robust. Control of HIV replication: Viral set point during the asymptomatic phase is a predictor of HIV progression and a commonly used outcome variable Figure 1. However, caution is required in comparing the extreme tails of the distribution to each other since, for example, factors promoting rapid progression can be quite different than those involved associated with long term AIDS-free survival analogous to comparing infant mortality to centenarians.
Different design strategies are to compare the genotype distribution in the extreme group to a normal population or to a middle group showing median or average progression Table S1 online. Replication in independent, well-powered populations is the gold standard of validation. On the other hand, the curse of GWAS is high rate of false negatives. Separating noise from true signals in genome-wide studies will continue to be a challenge, but hopefully this barrier will be breached through international collaborations to increase power.
In studies involving many tests on one sample of the full population, the consequent stringent standards for significance make it likely that the first person to report a significant test the winner will also report an effect size much larger than is likely to be seen in subsequent replication studies.