HIV-1 protecting CCR5-Delta32 allele in medieval Poland.

CCR5-Delta32 is the mutation in the chemokine receptor CCR5 that gives its homozygous carriers nearly complete protections from HIV-1 infection. Restricted almost exclusively to Europe, the mutation is thought to have originated in the continent and risen in frequency to the present-day value of approximately 10% due to a selective advantage it gave its carriers. The mutation bearing allele was initially calculated to be approximately 1000 years old and pandemic diseases, such as Bubonic Plague or smallpox were postulated to have selected it. However, new reports appear, that question these hypotheses. Data from ancient DNA (aDNA) studies prove the mutation to be much older, as suggested by calculations based on newer genetic maps. In order to investigate if the plagues of the last millennium selected the allele, and add to the discussion on CCR5-Delta32 origin and age, we searched for the mutation in aDNA isolated from individuals whose skeletal remains were collected at archaeological sites in Poland, dated back to 11-14th centuries. The calculated mean frequency of the allele in medieval Poland (5.06% as compared to contemporary 10.26%), implies its longer than previously believed presence in European populations, and suggests that historic pandemics had little effect on its present-day frequency.     

Gene polymorphisms in CCR5, CCR2, SDF1 and RANTES among Chinese Han population with HIV-1 infection

Chemokines and chemokine receptors are crucial for immune response in HIV-1 infection. Although many studies have been done to investigate the relationship between chemokines and chemokine receptor gene polymorphisms and host’s susceptibility to HIV-1 infection, the conclusions are under debate. In the present study, a cohort of 287 HIV-1 seropositive patients, 388 ethnically age-matched healthy controls and 49 intravenous drug users (IDUs) HIV-1 exposed seronegative individuals (HESN) from Chinese Han population were enrolled in order to determine the influence of host genetic factors on HIV-1 infection. Seven polymorphisms on four known chemokines/chemokine receptor genes (CCR5Δ32, CCR5 m303, CCR5 59029A/G, CCR2 64I, RANTES −403A/G, RANTES −28C/G and SDF1 3′-A) were screened. CCR5Δ32 and CCR5 m303 were absent or infrequent in Chinese Han population, which may not be hosts’ genetic protective factors for HIV-1 infection. Our results showed the CCR5 59029A/G, CCR2 64I and SDF1 3′-A were not associated with host’s resistance to HIV-1 infection. The frequency of RANTES −403A allele was significantly lower in HIV-1 patients than in healthy blood donors (p = 0.0005) and HESN group (p = 0.035), which implied the association between A allele and reduced HIV-1 infection risk. Different genetic models were assessed to investigate this association (AA vs. GG + AG, OR = 0.38 95% CI, 0.22–0.65 p = 0.0004; A vs. G, OR = 0.66 95% CI, 0.52–0.84 p = 0.0006), which supported this association, either. The genotype and allele distribution of RANTES −28 between HIV-1 patients and healthy controls (genotype profile: p = 0.072; allele profile: p = 0.027) or HIV-1 seronegative group (genotype profile: p = 0.036; allele profile: p = 0.383) were both at the marginal level of significance, which were not observed after Bonferroni correction. All these results suggest the RANTES −403A may be associated with reduced susceptibility to HIV-1 infection, while the RANTES −28 locus not. By lack of the patients’ clinical information, whether these polymorphisms affect AIDS disease progression and their role in different HIV-1 infection routes could not performed in present study and needs to be assessed in ongoing studies.     

Homing defects of B cells in HIV-1 infected children impair vaccination responses

Background

Successful vaccinations rely on antibody responses. Chemokine receptors play an important role in B cell homing to differentiation niches. We assessed CXCR4, CXCR5 and CCR6 expression on B cells during HIV-1 infection and relate it to antibody responses against a HBV vaccine.

High intrapatient HIV-1 evolutionary rate is associated with CCR5-to-CXCR4 coreceptor switch

In approximately 70% of individuals infected with HIV-1 subtype B, the virus switches coreceptor use from exclusively CCR5 use (R5 virus) to either inclusion of or exclusively CXCR4 use (X4 virus) during infection. This switch is associated with an accelerated loss of CD4⁺ T-cells and a faster progression to AIDS. Despite intensive research, the mechanisms responsible for coreceptor switch remains elusive. In the present study, we investigated associations between viral evolutionary rate and selection pressure versus viral coreceptor use and rate of disease progression in eight patients with longitudinally sampled HIV-1 env V1–V3 sequences. By employing a Bayesian hierarchical phylogenetic model, we found that the HIV-1 evolutionary rate was more strongly associated with coreceptor switch than with rate of disease progression in terms of CD4⁺T-cell decline. Phylogenetic analyses showed that X4 variants evolved from R5 populations. In addition, coreceptor switch was associated with higher evolutionary rates on both the synonymous and non-synonymous substitution level, but not with dN/dS ratio rates. Our findings suggest that X4 viruses evolved from pre-existing R5 viral populations and that the evolution of coreceptor switch is governed by high replication rates rather than by selective pressure. Furthermore, the association of viral evolutionary rate was more strongly associated with coreceptor switch than disease progression. This adds to the understanding of the complex virus–host interplay that influences the evolutionary dynamics of HIV-1 coreceptor use.     

Genetic variation within the gene encoding the HIV-1 CCR5 coreceptor in two South African populations

Polymorphisms within the open reading frame as well as the promoter and regulatory regions can influence the amount of CCR5 expressed on the cell surface and hence an individual's susceptibility to HIV-1. In this study we characterize CCR5 genes within the South African African (SAA) and Caucasian (SAC) populations by sequencing a 9.2 kb continuous region encompassing the CCR5 open reading frame (ORF), its two promoters and the 3′ untranslated region. Full length CCR5 sequences were obtained for 70 individuals (35 SAA and 35 SAC) and sequences were analyzed for the presence of single-nucleotide polymorphisms (SNPs), indels and intragenic haplotypes. A novel SNP (+258G/C) within the ORF leading to a non-synonomous amino acid (Trp → Cys) change was detected in one Caucasian individual. Results demonstrate a high degree of genetic variation: 68 SNP positions, four indels, as well as the Δ32 deletion mutant, were detected. Seven complex putative haplotypes spanning the length of the sequenced region have been identified. These haplotypes appear to be extensions of haplotypes previously described within CCR5. Two haplotypes, SAA-HHE and SAC-HHE were found in high frequency in the SAA and SAC population groups studied (20.0% and 18.6%, respectively) and share four SNP positions suggesting an evolutionary link between the two haplotypes. Only one of the identified haplotypes, SAA/C–HHC, is common to both study populations but the haplotype frequency differs markedly between the two groups (8.6% in SAA and 52.9% in SAC). The two population groups show differences in both haplotype arrangement as well as SNP profile.     

Treatment of HIV-1 infected pregnant women

Since 1 January 2004, pregnant women in the Netherlands have been universally screened for HIV infection. Three HIV-infected, pregnant women aged 28, 24 and 33 years respectively, illustrate some of the problems that may be encountered in this situation, as well as the treatment options available to prevent the transmission of HIV from mother to child. The first patient had a positive antibody test early in pregnancy for which she did not need treatment, the second had a positive antibody test late in pregnancy and the third was seropositive and on medication, but had the wish to become pregnant. A vaginal delivery is possible when highly active antiretroviral therapy (HAART) of the mother is started in good time and the plasma HIV-RNA is < 400 copies/ml at the time of delivery. In this situation the risk of transmission is reduced to around 1%. However, if HIV infection is diagnosed late in pregnancy or, despite HAART, the plasma HIV-RNA is not expected to be < 400 copies/ml, an elective caesarean section is scheduled at 38 weeks of pregnancy. In all instances the neonate is treated for 28 days with antiretrovirals, as post-exposure prophylaxis. If a woman with a known HIV infection wants to become pregnant, the choice of antiretroviral regimen and when this is started is determined by her treatment history and the potential toxic effects of the medication on the foetus.     

Mycoplasmas in the urine of HIV-1 infected men

The aim of this study was determine the prevalence of Mycoplasma hominis, M. genitalium, M. fermentans, M. pirum, M. penetrans and Ureaplasma urealyticum in HIV-infected patients. Culture and PCR were used to detect six species of Mycoplasma in first-void urine of HIV-1 infected men. A total of 497 HIV/AIDS patients (age range 5-75 years, mean 37 years) were screened in the study. All presented positive for at least one kind of mycoplasma, especially U. urealyticum and M. hominis. Six mycoplasmas were significant in the homosexual contact and heterosexual contact groups. The distribution of M. hominis, M. penetrans, and M. pirum were significantly different in this four-transmission category. CD4+ cell count levels were lower in the AIDS-associated Mycoplasma-positive group than in the Mycoplasma-negative group (P<0.01). This study indicates that U. urealyticum, M. hominis and M. fermentans are prevalent in HIV-1-infected male patients. This may be an indication of whether mycoplasmas are co-factors in the progression of HIV disease.     

HIV-1感染者抗病毒治疗后HIV-1 DNA载量动力学变化及影响因素分析

目的:分析云南省德宏傣族景颇族自治州（德宏州）HIV感染者抗病毒治疗后HIV-1 DNA载量的动力学变化及影响因素,为HIV-1 DNA定量检测的临床应用提供参考依据。方法:研究对象来源于德宏州CDC建立的2009-2018年HIV新发感染队列,构建HIV-1 DNA载量随抗病毒治疗时间动力学变化曲线图。采用logis...     

天津市不同感染途径HIV-1感染者流行毒株亚型分析

目的 了解天津市HIV-1毒株的流行情况,比较不同感染途径HIV-1感染者中流行毒株的亚型分布.方法 采集100例感染途径已知的HIV-1感染者抗凝全血标本,提取DNA,用巢式聚合酶链式反应扩增病毒gag基因,并进行序列测定和亚型分析.结果 100份样品中,有87份样品被成功扩增出HIV-1的gag基因片段,通过系统进化分析,确定天津市HIV-1流行毒株分属4个亚型和重组型,其中CRF01 _AE比例最大,达59.77％(52/87),主要分布在通过同性和异性性传播的HIV-1感染者中,而在通过静注吸毒感染的HIV-1感染者中以CRF07_BC亚型为主.结论 天津市HIV-1流行株至少有4种基因亚型,且不同感染途径HIV-1感染者流行毒株的亚型分布略有不同,应加强对HIV-1毒株亚型变异的监测,及时调整防治策略.     

Evolution of HIV-1 encephalopathy in children

BACKGROUND: This study has been conducted on a series of HIV-1 infected children, with the aim of illustrating the features of encephalopathy onset, its evolution and its influence on life expectancy. The most useful exams for diagnosis are also outlined. METHODS: The perspective study lasted from January 1989 to June 1997. Forty six symptomatic patients, out of 142 seropositive children, were followed up in the Department of Paediatric and Adolescence Sciences of the University of Turin. The patients, now between 1 yr 2 mth and 13 yr 9 mth old, were born from HIV-1 seropositive mothers; seroreverters have been excluded. Scheduled neuropsychiatric consultations were used, consisting of a neurologic exam and an interview with parents, cognitive evaluations, EEGs, Evoked Potentials and CT scans. The results have been evaluated with log-rank test for the analysis of the survival curves. RESULTS: We found a significantly higher mortality rate in encephalopathic versus non encephalopathic patients; encephalopathic patients, in whom neurologic signs began in the first year of life, have a worse prognosis than the other patients, in whom encephalopathy appeared later. We did not find a statistical correlation between clinical course and immunological deficit. The clinical features of encephalopathy are mainly characterized by pyramidal signs and cognitive deterioration. Clinical sign evolution is linked to the age of encephalopathy onset: plateau pattern encephalopathy, characterized by an early onset, severe motor signs and cognitive delay from the very beginning, shows a greater severity and a shorter survival than progressive encephalopathy, characterized by a slowly progressive evolution of pyramidal signs, to which a cognitive deterioration may be added. CONCLUSIONS: Neuropsychological exams can be helpful in the diagnosis and follow-up of encephalopathy.     

不同途径感染人群HIV-1亚型分布

目的 了解河北省石家庄市不同感染人群人类免疫缺陷病毒I型(HIV-1)亚型及分布特点。方法 从石家庄市报告的148例HIV-1抗体阳性者抗凝全血中提取前病毒DNA,用套式聚合酶链反应(nested-PCR)扩增病毒膜蛋白(ENV)基因的C2-V3区并进行序列测定,与国际标准参考序列比较确定亚型。结果 148例样品分属8个亚型,45例为欧美B,37例为CRF07-BC,35例为泰国B(B'),25例为CRF01-AE,C和CRF02-AG各2例,CRF03-AB和CRF11-CPX各1例。结论 既往供受血人员和注射吸毒人群感染的HIV-1亚型相对单一,性传播亚型分布较广。     

Immunogenicity and immunological memory induced by a 7-valent pneumococcal CRM197 conjugate vaccine in symptomatic HIV-1 infected children

A 7-valent CRM197 conjugate pneumococcal vaccine (PCV)-induced immune response were evaluated in all Greek symptomatic HIV-1 infected children and 21 age-matched controls. PCV immunogenicity was inferior in HIV patients compared with the controls although differences in geometric mean concentrations (GMC) were not significant (P>.05). Immune responses were strikingly different after anamnestic immunization, given in all study subjects, 12 months later. HIV-positive children achieved lower GMC for all serotypes compared with the controls (P=.002) and avidity for all except serotype 6B was inferior compared to baseline. Long-term PCV effectiveness is expected to be reduced among symptomatic HIV-1 infected children.     

HIV-1感染者免疫学及血清学指标检测

目的 了解人类免疫缺陷病毒I型(HIV-1)感染者体内免疫学、血清学指标变化在疾病发展中的作用。方法 应用免疫印迹实验(WB)、酶联免疫吸附试验(ELISA)和流式细胞仪检测61例HIV感染者和56例艾滋病(AIDS)患者外周静脉血中的抗体、吸光度A值、T淋巴细胞亚群。结果 HIV感染者和AIDS患者的CD₄⁺(P<0.0001)、CD₄⁺/CD₈⁺(P<0.0001),差异均有统计学意义。AIDS患者组中CD₄⁺与CD₈⁺(P=0.0051,r=0.369)呈正相关关系。HIV感染者CD₄⁺与CD₈⁺(P=0.239,r=0.153)无相关关系。结论 不同病期的HIV感染者抗体、T淋巴细胞亚群指标明显不同,该项指标检测可为HIV感染者的临床分期、判断预后和治疗提供依据。