SNP rs688 within the low-density lipoprotein receptor (LDL-R) gene associates with HCV susceptibility.

BACKGROUND & AIMS: Despite high-risk behaviour, 10%-20% of HCV multiple exposed individuals remain uninfected (MEU), whilst the remainder become infected (MEI). We hypothesize that host factors play a role in HCV susceptibility. We aimed to identify polymorphisms in host genes that encode for proteins involved in viral entry: CD81, Scavenger receptor 1 (SR-1), Low-density lipoprotein receptor (LDL-R), Claudin-1 (CLDN1), Occludin (OCLN) and Niemann-Pick C1-like 1 (NPC1L1). METHODS: Multiple exposed infected and MEU from two observational cohorts were selected. From the MSM study of acute infection with HCV (MOSAIC), HIV-1 infected MEU cases (n = 30) and HIV-1 infected MEI controls (n = 32) were selected based on reported high-risk behaviour. From the Amsterdam Cohorts Studies (ACS) injecting drug users (IDU) cohort, MEU cases (n = 40) and MEI controls (n = 22) were selected who injected drugs for ≥2 years, in the nineties, when HCV incidence was high. Selected single nucleotide polymorphisms (SNPs) were determined by sequencing or SNP assays. RESULTS: No associations were found for SNPs within genes coding for CD81, SR-1, Claudin-1 or Occludin between the MEU and MEI individuals from either cohort. We did observe a significant association for rs688 within the LDL-R gene with HCV infection (OR: 0.41 P = 0.001), however, LDL cholesterol levels did not vary between individuals carrying the differential SNPs. Additionally, a marginal significant effect was found for rs217434 and rs2072183 (OR: 2.07 P = 0.032 and OR: 1.76 P = 0.039, respectively) within NPC1L1. CONCLUSIONS: Our results demonstrate that the rs688 SNP within the LDL-R gene associates with HCV susceptibility through mucosal as well as intravenous exposure.

The role of a mutant CCR5 allele in HIV-1 transmission and disease progression.

A 32-nucleotide deletion (delta 32) within the beta-chemokine receptor 5 (CCR5) gene has been described in subjects who remain uninfected despite extensive exposure to HIV-1. This allele was found to be common in the Caucasian population with a frequency of 0.0808, but was not found in people of African or Asian ancestry. To determine its role in HIV-1 transmission and disease progression, we analyzed the CCRS genotype of 1252 homosexual men enrolled in the Chicago component of the Multicenter AIDS Cohort Study (MACS). No infected participant was found to be homozygous for the delta 32 allele, whereas 3.6% of at-risk but uninfected Caucasian participants were homozygous, showing the highly protective role of this genotype against sexual acquisition of HIV-1. No evidence was found to suggest that heterozygotes were protected against HIV-1 infection, but a limited protective role against disease progression was noted. The delta 32 allele of CCR5 is therefore an important host factor in HIV-1 transmission and pathogenesis.

HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China.

INTRODUCTION: In recent years, with the development of molecular epidemiology, molecular transmission networks based on evolutionary theory and sequence analysis have been widely used in research on human immunodeficiency virus (HIV)-1 transmission dynamics and precise intervention for high-risk populations. The HIV-1 molecular transmission network is a new method to study the population's access to the network, the characteristics of clustering, and the characteristics of interconnection in the network. Here, we analyzed the characteristics of the HIV-1 molecular transmission network of sexually transmitted people in Liaoning Province. METHODS: A study of HIV-infected persons who were sexually transmitted in Liaoning Province from 2003 to 2019. HIV-1 RNA was extracted, amplified and sequenced, and a phylogenetic tree was constructed to determine the subtype using the well matched pol gene region sequence. The gene distance between sequences was calculated, the threshold was determined, and the molecular transmission network was constructed. RESULTS: 109 samples of pol gene region were obtained. The main subtype of HIV-1 was CRF01_AE, followed by B, CRF07_BC, etc. 12.8% of them were resistant to HIV. At the threshold of 0.55 gene distance, 60.6% of them entered the HIV-1 molecular transmission network. Workers, sample source voluntary counseling and testing, other testing, subtype B and drug resistance are the factors influencing the access to HIV-1 molecular transmission network. The subtype of CRF01_AE formed 6 clusters in the molecular transmission network. In the network, the difference of connection degree between different subtypes was statistically significant. DISCUSSION: The three subtypes CRF01_AE, CRF07_BC and B that enter the molecular transmission network do not have interconnections, and they form clusters with each other. It shows that the risk of transmission among the three subtypes is less than the risk of transmission within each subtype. The factors affecting HIV-1 entry into the molecular transmission network were occupation, sample source, genotype and drug resistance. The L33F mutation at the HIV-1 resistance mutation site constitutes the interconnection in the largest transmission cluster in the network. The epidemiological characteristics of HIV-infected persons in each molecular transmission cluster show that 97% of the study subjects come from the same area and have a certain spatial aggregation. CONCLUSION: Constructing a molecular transmission network and conducting long-term monitoring, while taking targeted measures to block the spread of HIV can achieve precise prevention and control.

Evolution of sexually transmitted and sexually transmissible human herpesviruses.

Herpesviruses occur in an impressively wide range of animals and are associated with various diseases. The numerous routes taken during hundreds of millions of years of evolution have contributed to their striking adaptability and success as pathogens. Herpesviruses share a distinct virion structure and are classified taxonomically into a single order, the Herpesvirales, which is divided into three families. The phylogenetic relationships among members of the most populous family, the Herpesviridae, which includes all nine human herpesviruses, are generally similar to those among their hosts, supporting the view that there has been a large degree of coevolution between virus and host. Three human herpesviruses (human cytomegalovirus, Kaposi's sarcoma-associated herpesvirus, and herpes simplex virus type 1) are classed as agents capable of sexually transmissible infection (StxI), and one (herpes simplex virus type 2) as an agent capable of sexually transmitted infection (STI). The evolutionary characteristics of these viruses are described.

Local gene expression and immune responses of vaginal DNA vaccination using a needle-free injector.

The vaginal mucosa is the most common site of initiation of virus infections that are transmitted through heterosexual intercourse, including HIV and papillomavirus. Thus, in order to prevent or treat these infections, strong vaginal immunity is required as the first line of defense. In this study, to establish a less invasive, safe, convenient and effective immunization method, we examined the local (skin and vagina) gene transfection efficiency of a non-needle jet injector for daily insulin injection. In the skin experiment, the needle-free injector resulted in a marked increase in marker gene expression, compared to the conventional needle-syringe injection. In addition, intradermal DNA vaccination using the needle-free injector dramatically induced IFN-gamma and antibody systemic responses in mice. Furthermore, we investigated the applicability of the needle-free injector as a vaginal vaccination tool in rabbits. Vaginal gene expression using the needle-free injector was significantly greater than that using needle-syringe injection. Moreover, intravaginal vaccination by the needle-free injector promoted vaginal IgA secretion and IFN-gamma mRNA expression in the blood lymphocytes, to a degree significantly higher than that by needle-syringe injection. In conclusion, local vaginal DNA vaccination using a needle-free jet injector is a promising approach for the prevention and treatment of mucosal infectious diseases.

Immunization with adenovirus at the large intestinal mucosa as an effective vaccination strategy against sexually transmitted viral infection.

The large intestinal mucosa contains immunological structures that may potentially serve as a site for induction of mucosal immunity against infections. Adenovirus (Ad), which is effective in gene transfer to epithelia, may be an ideal antigen delivery system for vaccination at the large intestinal mucosa. To investigate this potential, we immunized mice with recombinant replication-deficient Ad through a single intracolorectal (ICR) administration. Effective transfer of encoded genes was found in both the epithelial layer and lamina propria of the colorectal mucosa. Dendritic cells were able to transfer antigen to the draining lymph nodes, where antigen-specific CD8(+) T cells were primed. Functional antigen-specific CD8(+) T cells and IgA-specific antibodies were detected during the effector phase in the large intestine. Compared to other immunization routes (intranasal, subcutaneous), ICR immunization induced stronger colorectal immune responses and more potent protection against rectal challenge with pathogenic viruses. Further, this immunization strategy provided vaginal protection, more potent than that induced by vaccination in the nose or skin. Therefore, large intestine mucosal immunization using Ad represents an effective vaccination strategy against virus infection at both rectal and vaginal mucosal tissue sites.

High prevalence of adeno-associated virus (AAV) type 2 rep DNA in cervical materials: AAV may be sexually transmitted.

Adeno-associated virus (AAV) is a human parvovirus that in laboratory and animal models has the ability to suppress the oncogenic phenotype of a variety of viruses and cellular derived oncogenes. The inhibitory effects of AAV have been mapped to its rap gene (Rep78 protein). Furthermore, seroepidemiologic data indicate that AAV infection is linked to reduced cervical cancer rates in humans. Because of AAV's inverse relationship with cervical cancer, we attempted to identify AAV rep sequences within DNA derived from cervical brushings taken from nondiseased middle class patients at a Little Rock clinic. Polymerase chain reaction (PCR) amplification was carried out with primers designed to amplify a specific segment of the endogenous human beta-globin gene or the AAV rep gene. Of those cervical samples that were positive for beta-globin DNA, 50% were also found to be positive for AAV rep DNA when analyzed by either ethidium bromide staining or dot-blot hybridization with an internal probe. These data strongly suggest that AAV is commonly carried in the genital region and further raise the possibility that AAV can be sexually transmitted.

Molecular epidemiologic analysis of Japanese patients with molluscum contagiosum.

BACKGROUND: Molluscum contagiosum virus (MCV) causes molluscum contagiosum (MC) in both children and adults. Recent studies have revealed that the DNA of MCV can be classified into two major types by restriction enzyme cleavage patterns; however, the relationship between MCV types and the clinical features has not been fully understood. Our study was conducted to examine whether there are geographic differences in the incidence of MCV types and whether a correlation exists between MCV types and the age, sex, and clinical status of the patients. METHODS: Specimens were obtained from 171 Japanese patients. The total DNA was extracted and digested with the restriction enzymes, BamH I, Hind III, and Cla I, respectively. Specimens were then electrophoresed in agarose gels. The gels were stained with ethidium bromide and photographs were taken under transillumination. RESULTS: Six different cleavage patterns were observed; they were classified into two major types, MCV 1 and MCV 2, consisting of two MCV 1-variants, and MCV 2 prototype, and three MCV 2-variants. The ratio of MCV 1 to MCV 2 was 13:1. MCV 1 was commonly detected in children (98%) and adult women (92%). MCV 2 was more frequently isolated from adult men (44%) and from patients with human immunodeficiency virus (HIV) infection (75%). CONCLUSION: MCV types found in Japanese children and adult women were predominantly MCV 1 and less frequently MCV 2. This pattern is similar to that observed in European countries and Australia, suggesting a high frequency and world-wide distribution of MCV 1. The higher incidence of MCV 2 among adult men and HIV-positive patients may indicate that transmission routes of MCV 1 and MCV 2 is somewhat different, of which the latter may be in part by sexual contact.

Atopy, anergic status, and cytokine expression in HIV-infected subjects.

BACKGROUND: In HIV infection T-cell dysfunction resulting in anergy and hypersensitivity reactions precedes T-cell depletion. A shift in the cytokine profile from a type 1 to a type 2 response has been postulated. OBJECTIVE: We sought to examine the cytokine expression patterns in HIV infection and the relationship to allergy, stage of HIV disease, and other laboratory parameters. METHODS: A cross-sectional analysis of IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p35, IL-13, and IFN-gamma mRNA expression in PBMCs by noncompetitive dot-blot PCR was performed on blood obtained from 18 HIV-infected subjects. Delayed-type hypersensitivity multitests to detect anergy, skin prick testing and in vitro assay for specific IgE antibodies, assay for total IgE, and enumeration of eosinophils, CD4(+), and CD8(+) T cells were also performed on all subjects. RESULTS: We found evidence of a decline in type 1 cytokines (IL-2, IL-12p35, and IFN-gamma) associated with AIDS, CD4(+) T cells less than 200/microL, anergy, and atopy, although this only reached statistical significance in anergy. There was no associated significant alteration in type 2 cytokines. CONCLUSIONS: This is the first report of an association between low constitutive in vivo expression of IL-12 mRNA and anergy, which supports earlier data from in vitro stimulation studies. The presence of atopy was associated with a more global reduction in cytokine expression. Because the decline in type 1 cytokines was not accompanied by a similar decline in type 2 cytokines, this does suggest a shift in the type 1/type 2 balance.