Parameters of human immunodeficiency virus infection of human cervical tissue and inhibition by vaginal virucides

Heterosexual transmission of human immunodeficiency virus (HIV) is the most frequent mode of infection worldwide. However, the immediate events between exposure to infectious virus and establishment of infection are still poorly understood. This study investigates parameters of HIV infection of human female genital tissue in vitro using an explant culture model. In particular, we investigated the role of the epithelium and virucidal agents in protection against HIV infection. We have demonstrated that the major target cells of infection reside below the genital epithelium, and thus HIV must cross this barrier to establish infection. Immune activation enhanced HIV infection of such subepithelial cells. Furthermore, our data suggest that genital epithelial cells were not susceptible to HIV infection, appear to play no part in the transfer of infectious virus across the epithelium, and thus may provide a barrier to infection. In addition, experiments using a panel of virucidal agents demonstrated differential efficiency to block HIV infection of subepithelial cells from partial to complete inhibition. This is the first demonstration that virucidal agents designed for topical vaginal use block HIV infection of genital tissue. Such agents have major implications for world health, as they will provide women with a mechanism of personal and covert protection from HIV infection.     

The cytokine network of acute HIV infection: a promising target for vaccines and therapy to reduce viral set-point?

Cytokines play a central role in the pathogenesis of many diseases, including HIV infection. However, the role of the cytokine network in early HIV infection is only now starting to be elucidated. A number of studies conducted in recent years have indicated that cytokines of the acute/early stages of HIV and SIV infection can impact viral set-point months later, and this is of critical importance since viral set-point during chronic HIV infection affects virus transmission and disease progression. This raises the question whether modulating the cytokine environment during acute/early HIV infection can be a target for novel approaches to develop a vaccine and therapeutics. In this review we focus on the kinetics and function of cytokines during acute HIV and SIV infection and how these may impact viral set-point. We also discuss unresolved questions that are essential for our understanding of the role of acute infection cytokines in HIV infection and that, if answered, may suggest novel therapeutic and vaccine strategies to control the worldwide HIV pandemic.     

Semen protects CD4+ target cells from HIV infection but promotes the preferential transmission of R5 tropic HIV

Sexual intercourse is the major means of HIV transmission, yet the impact of semen on HIV infection of CD4(+) T cells remains unclear. To resolve this conundrum, we measured CD4(+) target cell infection with X4 tropic HIV IIIB and HC4 and R5 tropic HIV BaL and SF162 after incubation with centrifuged seminal plasma (SP) from HIV-negative donors and assessed the impact of SP on critical determinants of target cell susceptibility to HIV infection. We found that SP potently protects CD4(+) T cells from infection with X4 and R5 tropic HIV in a dose- and time-dependent manner. SP caused a diminution in CD4(+) T cell surface expression of the HIVR CD4 and enhanced surface expression of the HIV coreceptor CCR5. Consequently, SP protected CD4(+) T cells from infection with R5 tropic HIV less potently than it protected CD4(+) T cells from infection with X4 tropic HIV. SP also reduced CD4(+) T cell activation and proliferation, and the magnitude of SP-mediated suppression of target cell CD4 expression, activation, and proliferation correlated closely with the magnitude of the protection of CD4(+) T cells from infection with HIV. Taken together, these data show that semen protects CD4(+) T cells from HIV infection by restricting critical determinants of CD4(+) target cell susceptibility to HIV infection. Further, semen contributes to the selective transmission of R5 tropic HIV to CD4(+) target cells.     

Differential expression in human and mouse cells of human immunodeficiency virus pseudotyped by murine retroviruses.

Expression of cell surface CD4 influences susceptibility of cells to human immunodeficiency virus (HIV) infection; however, some CD4-positive human and mouse cells are still resistant to HIV infection. To search for mechanisms of resistance to HIV independent of CD4 expression, HIV expression was studied in human and mouse cells normally resistant to HIV infection by introducing infectious virus by transfection of HIV DNA or infection with HIV pseudotyped with amphotropic or polytropic murine leukemia viruses. The results indicated that even when barriers to viral entry were bypassed, mouse NIH 3T3 cells and Dunni cells still showed a marked reduction in number of cells expressing HIV compared with the human cells studied, although the intensity of immunostaining of individual positive mouse cells was indistinguishable from that seen on permissive human cell lines. CD4 expression in mouse cells or human brain or skin cells did not influence the number of HIV foci observed after transfection with HIV DNA or infection with pseudotyped HIV. These results suggested that in addition to a block in the usual HIV fusion and entry process, CD4-positive mouse cells differed from human cells in exhibiting partial resistance to HIV infection which acted at a postpenetration step in the infection cycle. This resistance was partially overcome when mouse cells were infected by direct exposure to human lymphocytes producing HIV pseudotyped by amphotropic murine leukemia virus.     

Neisseria gonorrhoeae enhances infection of dendritic cells by HIV type 1

Clinical studies indicate that Neisseria gonorrhoeae (gonococci (GC)) has the capacity to enhance HIV type 1 (HIV-1) infection. We studied whether GC enhances HIV infection of activated dendritic cells (DCs). The results show that GC can dramatically enhance HIV replication in human DCs during coinfection. The GC component responsible for HIV infection enhancement may be peptidoglycan, which activates TLR2. TLR2 involvement is suggested by bacterial lipoprotein, a TLR2-specific inducer, which stimulates a strong enhancement of HIV infection by human DCs. Moreover, participation of TLR2 is further implicated because GC is unable to stimulate expression of HIV in DCs of TLR2-deficient HIV-1-transgenic mice. These results provide one potential mechanism through which GC infection increases HIV replication in patients infected with both GC and HIV.     

Strategic problems in counteracting the spread of HIV infection in the Altai Territory

The Altai Territory belongs at present to regions with the insignificant level of the spread of HIV infection. By December 1, 1999, the Altai Territory had 31 registered cases of HIV infection, which constituted 1.33 per 10,000 of the population (the corresponding figure for the whole of Russia being 14.92). But the situation with HIV/AIDS showed the general tendency to the development of the epidemic of HIV infection due to steady growth and the wide involvement of injecting drug users in the epidemic process. Before 1999 all cases of HIV infection registered in the Altai Territory were imported. Out of 31 HIV infected persons detected in the territory, 18 were injecting drug users. In 1999 local foci of HIV infection were formed among drug users in two big cities of the Altai Territory, which was indicative of the gradual transition of HIV infection from the phase of the registration of individual cases to the phase of the formation of local foci among some groups of the population.     

Tuberculosis in patients with human immunodeficiency virus infection. Review of current concepts.

Tuberculosis is a frequent complication of human immunodeficiency virus (HIV)-induced immunosuppression. The diagnosis of extrapulmonary tuberculosis in patients with evidence of HIV infection qualifies as a criterion of the acquired immunodeficiency syndrome. Demographic characteristics of patients with tuberculosis and HIV infection vary by region and reflect the degree to which patients with Mycobacterium tuberculosis infection adopt behaviors that put them at risk for HIV infection. The clinical features of tuberculosis in patients with HIV infection are atypical. Extrapulmonary disease, tuberculin anergy, and unusual findings on chest radiographs occur most frequently when tuberculosis afflicts patients with other clinical evidence of HIV infection at the time tuberculosis is diagnosed. Treatment is effective for tuberculosis in HIV-seropositive patients, and isoniazid prophylaxis is recommended for HIV-infected patients with positive tuberculin skin tests.     

Use of a high resolution melting (HRM) assay to compare gag, pol, and env diversity in adults with different stages of HIV infection

Background

Cross-sectional assessment of HIV incidence relies on laboratory methods to discriminate between recent and non-recent HIV infection. Because HIV diversifies over time in infected individuals, HIV diversity may serve as a biomarker for assessing HIV incidence. We used a high resolution melting (HRM) diversity assay to compare HIV diversity in adults with different stages of HIV infection. This assay provides a single numeric HRM score that reflects the level of genetic diversity of HIV in a sample from an infected individual.

Methods

HIV diversity was measured in 203 adults: 20 with acute HIV infection (RNA positive, antibody negative), 116 with recent HIV infection (tested a median of 189 days after a previous negative HIV test, range 14–540 days), and 67 with non-recent HIV infection (HIV infected >2 years). HRM scores were generated for two regions in gag, one region in pol, and three regions in env.

Results

Median HRM scores were higher in non-recent infection than in recent infection for all six regions tested. In multivariate models, higher HRM scores in three of the six regions were independently associated with non-recent HIV infection.

Conclusions

The HRM diversity assay provides a simple, scalable method for measuring HIV diversity. HRM scores, which reflect the genetic diversity in a viral population, may be useful biomarkers for evaluation of HIV incidence, particularly if multiple regions of the HIV genome are examined.     

Infection of granulocyte/monocyte progenitor cells with HIV1

In order to study whether cytopathic HIV1 infection of haemopoietic progenitor cells is involved in the derangement of haemopoiesis in patients with HIV1 infection, we infected enriched progenitor cells with HIV1, by addition of viral inoculate supernatants from HIV1-infected peripheral blood mononuclear cells or by coculture with HIV1-infected monocytes/macrophages. Progenitor cells were seeded into colony assays and single colonies were chosen for HIV1 mRNA determination by in situ hybridization. Growth of progenitors was not affected by infection. However, up to 42% of colonies of pluripotent progenitor cells (colony-forming unit/granulocyte-erythrocyte-monocyte; CFU-GEM) and committed progenitor cells CFU/granulocyte-monocyte (CFM-GM) contained HIV1 mRNA-expressing cells.In addition, we studied HIV1 infection of progenitor cells from the bone marrow of 6 patients with AIDS or AIDS-related complex. Two patients were negative, two had a few colonies expressing HIV1 mRNA in a minority of cells, and in the remaining two, up to 11% of CFU-GM contained HIV1-expressing cells.Thus, infection of progenitor cells with HIV1 was achieved experimentally in vitro and occurs in vivo. However, growth of progenitors after in vitro infection continues and therefore HIV1 infection does not seem to contribute directly to the reduced incidence of haemopoietic progenitor cells in vivo.     

Prevention and control of HIV infection in the Osh region of the Kyrgyz Republic

A total of 178 cases of HIV infection were diagnosed in the Osh region of the Kyrgyz Republic for January 1, 2003, the intensity of the prevalence of HIV infection being 14.5 per 100,000 of the population with this figure for the whole republic being equal to 5.9. In the dynamics of the HIV infection epidemic two periods were detected. During the first 3 years (1998-2000) a few individual imported cases of HIV infection were registered in the region. During the last 2 years (2001-2002) 98.8% of all cases of HIV infection registered in the region, as well as the presence of an epidemic outbreak among injection drug users (IDU), were detected. The risk factors of getting HIV infection were the intravenous use of drugs and a low level of information among young people concerning the routes of transmission of this infection and means of protection from HIV/AIDS: the promotion of healthy life style among young people, the introduction of the programs of "harm reduction" among IDU and the rules of safe sex.     

The results of sentinel epidemiological surveillance on the level of HIV prevalence among injection narcotic abusers in the city of Poltava

The sentinel epidemiological surveillance on the level of spread of HIV infection among injecting drug users in Poltava, taking part in the program of harm reduction, was carried out. The results of the surveillance revealed that the level of HIV infection among drug users was 37.8%, the level of HIV infection among females being higher than that among males. These data indicate that the level of HIV infection rises with the increase of age and the time of drug consumption. Still in the age group of 30 years and older and among drug addicts using drugs for 7 years and longer the lowest level of HIV infection was noted.     

The breakdown of the cytokine network subsequent to human immunodeficiency virus infection

The acquired immunodeflciency syndrome (AIDS) is a clinically multifaceted disease induced by infection with the human immunodeficiency virus (HIV). HIV infection results in a complex pattern of immunologic alterations that leads to the development of AIDS in the majority of HIV seropositive (HIV+) individuals. The reduction in CD4 T lymphocyte counts is the hallmark of HIV infection; nevertheless, long before the reduction in CD4 counts reaches critical levels, a series of profound and complex defects that impair the function of CD4 T lymphocytes can be detected. Thus, HIV infection is characterized by quantitative and qualitative defects affecting CD4 T lymphocytes. It was suggested recently that programmed cell death (PCD) is an important mechanism leading to CD4 depletion in HIV infection, and that susceptibility of peripheral lymphocytes to PCD is differentially regulated by diverse cytokines. Thus, type 1 cytokines would protect CD4 lymphocytes against PCD, whereas type 2 cytokines would not protect against, and could augment, PCD. We suggest that the qualitative alterations of the immune response provoke the CD4 depletion characteristic of HIV disease via type 2 cytokinemediated augmentation of PCD, and are therefore ultimately responsible for the progression of HIV infection. Finally, we summarize recent data showing that three correlates of disease progression: emergence of HIV strains with syncitium-inducing ability (SI), type 1-to-type 2 cytokine shift, and CD4 depletion, are significantly associated, suggesting a complex interconnected virologic-immunologic pathogenesis of HIV infection.     

Altering cell death pathways as an approach to cure HIV infection

Recent cases of successful control of human immunodeficiency virus (HIV) by bone marrow transplant in combination with suppressive antiretroviral therapy (ART) and very early initiation of ART have provided proof of concept that HIV infection might now be cured. Current efforts focusing on gene therapy, boosting HIV-specific immunity, reducing inflammation and activation of latency have all been the subject of recent excellent reviews. We now propose an additional avenue of research towards a cure for HIV: targeting HIV apoptosis regulatory pathways. The central enigma of HIV disease is that HIV infection kills most of the CD4 T cells that it infects, but those cells that are spared subsequently become a latent reservoir for HIV against which current medications are ineffective. We propose that if strategies could be devised which would favor the death of all cells which HIV infects, or if all latently infected cells that release HIV would succumb to viral-induced cytotoxicity, then these approaches combined with effective ART to prevent spreading infection, would together result in a cure for HIV. This premise is supported by observations in other viral systems where the relationship between productive infection, apoptosis resistance, and the development of latency or persistence has been established. Therefore we propose that research focused at understanding the mechanisms by which HIV induces apoptosis of infected cells, and ways that some cells escape the pro-apoptotic effects of productive HIV infection are critical to devising novel and rational approaches to cure HIV infection.     

HIV infection epidemic in Russian Federation and its features at the present stage

The problem of HIV infection spread in Russian Federation is examined in the article. Data on HIV infection dynamics and predominate risk groups of the population during different years are presented. Age structure of HIV infected individuals in Russian Federation is examined. Main factors that promote HIV infection spread in Russian Federation are specified and means of control are proposed.     

Comparative analysis of the serum microbiome of HIV infected individuals

HIV infects the CD4 cells which marks the suppression of our immune system. DNA from serum of healthy, treated and untreated HIV infected individuals was extracted. The DNA was subjected to 16S metagenomic sequencing and analyzed using QIIME2 pipeline. 16S sequencing analysis showed serum microbiome was dominated by Firmicutes, Proteobacteria, Bacteroidota and Actinobacteria. Treated HIV infection showed highest abundance of Firmicutes (66.40%) significantly higher than untreated HIV infection (35.88%) and control (41.89%). Bacilli was most abundant class in treated (63.59%) and second most abundant in untreated (34.53%) while control group showed highest abundance of class Gamma-proteobacteria (45.86%). Untreated HIV infection group showed Enterococcus (10.72%) and Streptococcus (6.599%) as the most abundant species. Untreated HIV infection showed significantly higher (p = 0.0039) species richness than treated and control groups. An altered serum microbiome of treated HIV infection and higher microbial abundance in serum of untreated HIV infection was observed.     

Transmission of the human immunodeficiency virus during breast feeding and heterosexual contacts

Two cases of the transfer of HIV infection are described: a child got HIV infection through breast feeding from the mother infected with HIV as the result of blood transfusion made 2 weeks after the birth of the child and 2 men were infected with HIV as the result of sexual relations with a woman found to be a HIV carrier.     

Differential effects of migration and deportation on HIV infection among male and female injection drug users in Tijuana, Mexico

HIV prevalence is rising, especially among high risk females in Tijuana, Baja California, a Mexico-US border city situated on major migration and drug trafficking routes. We compared factors associated with HIV infection among male and female injection drug users (IDUs) in Tijuana in an effort to inform HIV prevention and treatment programs. IDUs aged > or = 18 years were recruited using respondent-driven sampling and underwent testing for HIV, syphilis and structured interviews. Logistic regression identified correlates of HIV infection, stratified by gender. Among 1056 IDUs, most were Mexican-born but 67% were born outside Tijuana. Reasons for moving to Tijuana included deportation from the US (56% for males, 29% for females), and looking for work/better life (34% for females, 15% for males). HIV prevalence was higher in females versus males (10.2% vs. 3.5%, p = 0.001). Among females (N = 158), factors independently associated with higher HIV prevalence included younger age, lifetime syphilis infection and living in Tijuana for longer durations. Among males (N = 898), factors independently associated with higher HIV prevalence were syphilis titers consistent with active infection, being arrested for having 'track-marks', having larger numbers of recent injection partners and living in Tijuana for shorter durations. An interaction between gender and number of years lived in Tijuana regressed on HIV infection was significant (p = 0.03). Upon further analysis, deportation from the U.S. explained the association between shorter duration lived in Tijuana and HIV infection among males; odds of HIV infection were four-fold higher among male injectors deported from the US, compared to other males, adjusting for all other significant correlates (p = 0.002). Geographic mobility has a profound influence on Tijuana's evolving HIV epidemic, and its impact is significantly modified by gender. Future studies are needed to elucidate the context of mobility and HIV acquisition in this region, and whether US immigration policies adversely affect HIV risk.     

Is HIV infection associated with an increased risk for cholera? Insights from a mathematical model

Cholera, a waterborne gastroenteric infection, remains a significant threat to public health in sub-Saharan Africa, the region most heavily affected by HIV. It is biologically plausible that immune suppression caused by HIV infection predisposes to cholera. In this paper, a simple mathematical model is developed and comprehensively analyzed to assess whether HIV infection is associated with an increased risk for cholera or not. Analytical results of the model show that the quantities R(c) and R(h), which represents the reproductive number for cholera and HIV infection, respectively, provide threshold conditions that determine cumulative new single and dual infection cases. These threshold conditions can be used to gain important insights on the epidemiological consequences of HIV and cholera coexistence in the community. Numerical results are provided to support the analytical findings. The findings suggest that in a cholera-endemic area, HIV infection is associated with an increased risk for cholera.     

我国男男性行为人群中人类免疫缺陷病毒感染疫情特点及防治策略

目前我国人类免疫缺陷病毒（HIV）感染疫情总体处于低流行水平,但男男性行为（MSM）人群中HIV感染呈现快速上升趋势,传播亚型呈现出新的特点,疾病进展较快。HIV核酸及抗原抗体检测等手段对早期发现MSM人群中HIV感染者具有重要意义。解析MSM人群艾滋病疾病进展的影响因素,发现新的生物学标记,可为早期评估HIV感染的预后提供创新性手段。早期发现我国MSM人群中HIV感染者和抗病毒治疗等综合干预,对我国艾滋病流行的控制具有重要意义。     

Infection of monocytes/macrophages by HIV in vitro

Because of the very important role of the mononuclear phagocyte system in the immunopathogenesis of HIV infection, a culture system for in vitro studies of infection of monocytes/macrophages with HIV was developed. A method is described for the infection of human monocytes/macrophages cultured on hydrophobic membranes (Teflon) with different strains of HIV. The HIV isolates can be characterized according to their replication potential on monocyte/macrophages cultures. The biological properties of some HIV1 and HIV2 isolates are compared in lymphocyte and monocyte/macrophage cultures.