AIDS research and human retroviruses最新文献

The global human immunodeficiency virus 1 (HIV-1) pandemic is driven by the extraordinary genetic diversity of the virus, largely resulting from frequent recombination events. These events generate circulating recombinant forms (CRFs) and unique recombinant forms, which significantly contribute to the complexity of HIV-1 epidemiology, especially within key populations, such as men who have sex with men (MSM). Here, we identified three novel HIV-1 recombinant strains consisting of the CRF01_AE and CRF07_BC subtypes from HIV-positive MSM in Baoding City, Hebei Province, China. Using near-full-length genome analysis and phylogenetic reconstruction, the strains-designated BDL017, BDL036, and BDSB006-were shown to exhibit distinct mosaic structures. Each strain contained multiple inserted fragments from CRF07_BC and CRF01_AE within various genomic regions, highlighting their complex recombination patterns. Our study emphasizes the need for continuous molecular surveillance among MSM in Hebei Province to monitor these recombinant forms and prevent their spread to the broader population.

In this study, by analyzing the available near full-length genome (NFLG) sequences of CRF55_01B, it was found that two of the NFLG sequences could not be clustered with other NFLG sequences. Recombination analysis and phylogenetic analysis suggested that these two NFLG sequences arose by recombination with subtype B based on CRF55_01B, rather than by recombination directly derived from CRF01_AE and subtype B. In addition, two other HIV-1 partial gene fragments found in the database shared the same characteristics as these two NFLG sequences in the key recombination region. These sequences may therefore represent a previously unrecognized circulating recombinant form (CRF), which has been named CRF149_01B. Evolutionary analyses suggested that CRF149_01B emerged between approximately 2005 and 2007. The discovery of CRF149_01B highlights the complexity of HIV recombinant evolution and advances the refinement of the HIV genotyping system. A deeper understanding of HIV-1 genetics will facilitate molecular tracing and provide a basis for studying the biological properties of HIV.

Acquired immune deficiency syndrome caused by human immunodeficiency virus (HIV) is a serious infectious disease because of its' high genetic variability. Nowadays, homosexual contact has become the most predominant transmission route in Hebei province, China, leading to the emergence of novel HIV-1 recombinant forms. The neighbor-joining (N-J) phylogenetic trees were constructed using MEGA 6.0 in order to identify the subtypes of H22063 and H22144. Recombination breakpoints were identified using online resources jpHMM, RIP 3.0, and Simplot 3.5.1. In this study, we identified two novel HIV-1 unique recombinant forms (URFs) _0107 from three men who have sex with men in Hebei province, including H22063 and H22144. The near full-length genome analysis showed H22063 has seven gene recombination sub-regions, including three subtype CRF07_BC gene fragments inserted into the CRF01_AE backbone. H22144 has nine gene recombination sub-regions, including four subtype CRF07_BC gene fragments inserted into the CRF01_AE backbone. This study confirms the emergence of novel recombinant forms and suggests we should strengthen the monitoring of novel HIV recombinant forms in order to deal with the complex HIV-1 epidemiological trend in Hebei province, China.

Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) provides an effective treatment option for people with HIV (PWH). Studies suggest that PWH on LAI CAB/RPV may experience isolated episodes of transient viremia (HIV RNA > 20 copies/mL) defined as virologic blips (VB). The risk factors for VB in PWH receiving LAI CAB/RPV are limited. We aimed to describe a cohort of PWH on LAI CAB/RPV and evaluate risk factors and time to VB following LAI CAB/RPV initiation. We obtained DC Cohort data from PWH who initiated LAI CAB/RPV prior to July 2023 and used Kaplan-Meier curves and Cox proportional hazards models to evaluate the association between participant demographics, HIV clinical factors, and time to VB. Among 98 PWH who initiated LAI CAB/RPV, 9 (9.2%) experienced at least one VB (median HIV RNA = 50 copies/mL; ranges 30-12,000 copies/mL) during a median follow-up period of five months (IQR: 2-10). The median CD4 count among PWH was 754 cells/µL (IQR: 598, 980) at the time of LAI CAB/RPV initiation. Having a high CD4 (≥ 500 cells/μL) at LAI CAB/RPV initiation was significantly associated with a lower hazard for VB when compared to baseline CD4 < 200 cells/µL [hazard ratios (HR): 0.15 [95% confidence intervals (CI): 0.03, 0.77]; aHR: 0.07 (95% CI: 0.01, 0.50); log-rank p = .026]. No other characteristics were significantly associated with time to VB, and no participants experienced virologic failure. Considerations for baseline CD4 may be important when initiating a patient on LAI CAB/RPV, and future studies will help evaluate the VB occurrence and associated factors among PWH.

Under the background of the main epidemic HIV strains (CRF01_AE and CRF07_BC) co-circulation in China, more HIV second-generation recombinant (SGR) strains with CRF01_AE and CRF07_BC as the backbone were also emerging. In this study, we characterize a novel HIV-1 second-generation circulating recombinant form (CRF117_0107) consisting of CRF01_AE and CRF07_BC fragments from three epidemiologically unrelated individuals infected with HIV-1. One near full-length genome (NFLG) sequence was amplified, sequenced, and spliced in two halves using RNA extracted from the plasma of a homosexual in Shenzhen, Guangdong Province. Two other NFLG sequences were obtained from the Los Alamos HIV Sequence Database under accession numbers KY201177 and MK397789, which were isolated from men who have sex with men (MSM) in Guangdong Province and Zhejiang Province, respectively. Phylogenetic analysis revealed that these NFLG sequences formed a monophyletic cluster with a high bootstrap value of 1.0. Recombination analysis demonstrated that the genome of CRF117_0107 was separated into three segments by two breakpoints. Further subregional phylogenetic analysis was performed that showed segment I+III (790-5990nt, 8295-9412nt) of CRF117_0107 originated from the CRF07_BC cluster, and Segment I+III (5991-8294nt) originated from the CRF01_AE cluster. The appearance of CRF117_0107 further highlights that HIV-1 SGR strains containing CRF01_AE and CRF07_BC will be generated more frequently and will most likely be more conducive to accelerating the spread of HIV in China. This study suggested it's essential to monitor HIV-1 second-generation CRFs among high-risk populations such as MSM for the epidemic and evolution dynamics of HIV-1 in China.

The objective of this study was to estimate the structure and relationships between four h ypothesized frailty dimensions (physical, emotional, cognitive, and social) and the extent to which personal and HIV-related factors and comorbidity associate with these frailty dimensions. This is a secondary analysis of an existing dataset arising from Positive Brain Health Now study (n = 856) in people aging with HIV (mean age: 52.3 ± 8.1 years). Structural equation modeling (SEM) models were applied to two cross-sections of the data: one at study entry and one at second visit, 9-month apart. Multidimensional frailty was modeled based on the combined Wilson-Cleary and International Classification of Functioning, Disability and Health framework. Four dimensions were operationalized with patient-reported and self-report measures from standardized questionnaires. The SEM model from the first visit was replicated using data from the second visit, testing measurement invariance. The proposed model showed acceptable fit at both visits (including no violation of measurement invariance). The final model for the first visit showed that sex, body mass index, HIV diagnosis pre-1997, current or nadir CD4 counts, and comorbidity did not associate with any frailty dimension; however, age (β range: 0.12-0.25), symptoms (β range: -0.35 to -0.58), and measured cognition (β range: 0.10-0.24) directly associated with all frailty dimensions. The model remained stable across the two visits. This study contributes evidence for operationalizing multidimensional frailty. Evidence-based interventions are available for many of the measures considered here, offering opportunities to improve the lives of people with frailty in the context of HIV.

As the number of older people with HIV (PWH) grows, accidental falls and their associated negative health outcomes are of increasing concern. Fall risk can be measured using novel screening tools such as evaluating postural stability using force plate technology. The aims of this study were to test this technology to assess fall risk among older PWH. In a cross-sectional, observational study of people without HIV (PWoH) with a range of fall risk, participants underwent balance assessment using the validated BTrackS balance plate. Postural stability was compared by HIV serostatus. Multivariable linear regressions were used to examine the relationship between postural stability and validated measures of fall risk balance and frailty status. Among 34 PWH and 30 PWoH, all ≥50 years, postural stability was worse among PWH (35.4 cm vs. 28.3 cm, p = .07). In multivariable models, worse postural stability was associated with reporting a fall in the past 6 months (β = 0.32, p = .004), worse fall efficacy (β = 0.45, p < .001), and being frail or prefrail (β = 0.26, p = .027). In multivariable models stratified by HIV serostatus, worse postural stability was significantly associated with worse fall efficacy (β = 0.53, p < .01) and lower balance confidence (β = -0.33, p =. 04) among PWH but not PWoH. Among older PWH and PWoH, worse postural stability was associated with validated measures of fall risk, including history of falls and poorer fall efficacy. Assessment of postural sway is a promising objective screening test for fall risk among older PWH.

Despite advancements in antiretroviral therapy (ART) that reduces the viral load to undetectable levels and improve CD4 T cell counts, viral eradication has not been achieved due to HIV-1 persistence in resting CD4⁺ T-cells. We, therefore, characterized the tat gene, which is essential for HIV-1 replication and pathogenesis, from 20 virologically controlled aging individuals with HIV (HIV⁺) on long-term ART and improved CD4⁺ T-cell counts, with a particular focus on older individuals. Peripheral blood mononuclear cell genomic DNA from HIV⁺ were used to amplify tat gene by polymerase chain reaction followed by nucleotide sequencing and analysis. Phylogenetic analysis showed that each HIV⁺ tat sequences were confined to their own subtrees and well discriminated from other HIV⁺ sequences. Moreover, there was a low degree of viral heterogeneity and lower estimates of genetic diversity within these individuals' tat sequences, which decreased with increasing CD4 T counts in these HIV⁺. Most HIV⁺ Tat deduced amino acid sequences showed intact open reading frames and maintained the important functional domains for Tat functions, including transactivation, TAR binding, and nuclear localization. Furthermore, Tat-deduced amino acid sequences showed variation in previously characterized cytotoxic T lymphocytes (CTL) epitopes, suggesting escape mutants. In conclusion, a low degree of genetic variability and conservation of functional domains and variations in CTL epitopes were the features of tat sequences that may be contributing to viral persistence in these 20 aging individuals with HIV on long-term ART.

Human T cell lymphotropic virus type 1 (HTLV-1) is associated with adult T cell leukemia/lymphoma (ATLL), a fetal malignant infection. Recently, HTLV-1 new asymptomatic carriers (ACs) have frequently been reported among blood donors. Reaching the profound concept of HTLV-1-associated molecular pathogenesis could result in finding novel therapeutic strategies. The current study aimed to determine leukemia-related signaling regulation in ATLL. Thirty participants were evaluated in 3 groups, including 10 ATLL patients, 10 ACs, and 10 normal controls. Blood samples were isolated without any chemotherapy history from ATLL patients. Also, blood samples were recovered from ACs and normal individuals. White blood cells isolation was done on the collected blood samples. After this, RNA was extracted from the prepared samples and used for the cDNA synthesis. TAX and HTLV-1 basic leucine zipper factor as viral genes and cellular genes, including MKP-1, EVI-1, JNK-1, FOXO-1, AKT-1, DEPTOR, MTOR, and JUN, were investigated using real-time PCR. The mean age of ATLL patients was 53.2 ± 7.32 years, and 9 (90%) were male. The EVI-1 and FOXO-1 expression levels were significantly associated with ATLL patients compared with the internal control. However, the significant differences in expression of other genes in the remaining groups were not seen. Discovering viral and cellular signaling pathways that regulate HTLV-1 transformation is essential. A novel therapeutic strategy for ATLL-regulating cellular signaling pathways in vivo could be considered. Therefore, clinical trials using activators and inhibitors of related cellular signaling pathways for cell therapy of ATLL are recommended. It is recommended that more investigation be conducted on FOXO-1 and EVI-1 to target these genes and reveal the molecular pathogenesis of ATLL.

During male-to-female transmission, HIV-1 must cross the mucosal epithelium of the female reproductive tract to gain access to underlying target cells. Previously, we demonstrated that HIV-1 can penetrate intact columnar and squamous genital epithelia in both ex vivo and in vivo systems. We found that the virus enters the squamous epithelium via a diffusion-based mechanism, but the mechanism of entry in columnar epithelium remained elusive. Using a similar set of approaches, we now demonstrate that HIV enters the endocervical simple columnar epithelium via endocytosis. By exposing human endocervical explant tissue to small molecule endocytosis inhibitors prior to virus exposure, we show that virus penetration into the simple columnar barrier is impeded. These data suggest a transcytosis-based mechanism for HIV-1 penetration into the endocervical columnar barrier.