Virus In Individuals Research Articles

Longitudinal study on oral shedding of herpes simplex virus 1 and varicella‐zoster virus in individuals infected with HIV

Primary herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) infection leads to a life-long latent infection of ganglia innervating the oral mucosa. HSV-1 and VZV reactivation is more common in immunocompromised individuals and may result in viral shedding in saliva. We determined the kinetics and quantity of oral HSV-1 and VZV shedding in HSV-1 and VZV seropositive individuals infected with HIV and to assess whether HSV-1 shedding involves reactivation of the same strain intra-individually. HSV-1 and VZV shedding was determined by real-time PCR of sequential daily oral swabs (n = 715) collected for a median period of 31 days from 22 individuals infected with HIV. HSV-1 was genotyped by sequencing the viral thymidine kinase gene. Herpesvirus shedding was detected in 18 of 22 participants. Shedding of HSV-1 occurred frequently, on 14.3% of days, whereas solely VZV shedding was very rare. Two participants shed VZV. The median HSV-1 load was higher compared to VZV. HSV-1 DNA positive swabs clustered into 34 shedding episodes with a median duration of 2 days. The prevalence, duration and viral load of herpesvirus shedding did not correlate with CD4 counts and HIV load. The genotypes of the HSV-1 viruses shed were identical between and within shedding episodes of the same person, but were different between individuals. One-third of the individuals shed an HSV-1 strain potentially refractory to acyclovir therapy. Compared to HSV-1, oral VZV shedding is rare in individuals infected with HIV. Recurrent oral HSV-1 shedding is likely due to reactivation of the same latent HSV-1 strain.

An HIV Type 2 Case Series in Italy: A Phylogenetic Analysis

In recent years, the increase of migration from countries where human immunodeficiency virus type 2 (HIV-2) is endemic to industrialized countries has facilitated the spread of the virus in individuals previously unexposed to this threat. In this report, we performed a phylogenetic analysis on pol and env sequences of HIV-2 strains identified in foreigners and native citizens to trace the origin of infection. All but one of the 17 pol gene sequences were classified as group A. HIV-2 strains were aggregated in several clusters depending by the country of origin and/or infection. One patient (1AA) was classified as being infected with a recombinant between HIV-2 group A and HIV-2 group B, because the pol gene sequence was clearly in the group A, but an env V3 region sequence from this patient was more similar to group B viruses. Therefore, it is urgent to strengthen the surveillance and use adequate molecular virological tools to diagnose and monitor HIV-2 infection.

Tracking replication-competent HIV reservoirs in infected individuals

Prolonged suppression of plasma viremia is now achievable in a majority of HIV-infected individuals receiving antiretroviral therapy (ART). However, ART alone cannot eradicate HIV in infected individuals. The purpose of this review is to discuss the importance of tracking levels of infected CD4(+) T cells carrying replication-competent HIV in basic and clinical research and how the use of this virologic marker could help determine the efficacy of ART and several novel therapeutic strategies that are being proposed for eliminating persistent viral reservoir in infected individuals receiving ART. In recent years, there has been a growing interest within the HIV/AIDS scientific community to develop therapeutic strategies aimed at eliminating persistently infected CD4(+) T cells in order to achieve a cure for HIV in infected individuals receiving ART. These approaches include administration of HIV-activating agents, modification of the genetics of CD4(+) T cells, stem cell transplantation, and therapeutic vaccination. Such approaches would ultimately require careful and accurate assessments of the effect of therapeutic agents on HIV burden in infected individuals. Given that the majority of infected CD4(+) T cells in vivo carry replication-defective HIV, longitudinal measurements of the frequency of cells carrying replication-competent HIV along with other quantitative virologic parameters, such as levels of plasma viremia and cell-associated viral nucleic acid, can provide critical insight into the dynamics of the persistent viral reservoirs. Information related to HIV pathogenesis and the feasibility of eradicating the virus in infected individuals receiving ART in combination with novel therapeutic agents can also be gained from these analyses.

Reactivation of latent viruses in individuals receiving rituximab for new onset type 1 diabetes

BackgroundRituximab has been successfully used as an experimental therapy in different autoimmune diseases. Recently, a double-blind placebo-controlled phase-2 study in early onset type 1 diabetes showed that rituximab delayed progression of the disease. However, like with any immunosuppressive therapy, there is a concern of opportunistic viral reactivations with the use of rituximab, including herpes and polyomaviruses. ObjectivesTo study the incidence of new infections and reactivations with BK, JC, Epstein–Barr and cytomegalovirus (BKV, JCV, EBV and CMV) in T1D participants in the phase-2 rituximab study. Study designSubjects received 4 weekly doses of rituximab (N=57) or placebo (N=30) during the first month of study. Blood samples obtained at weeks 0, 12, 26, 56 and 78 were assayed for CMV, EBV, BKV and JCV by real-time DNA PCR and serology. ResultsEBV reactivations were diagnosed by PCR in 25% of placebo, but none of rituximab recipients (p<0.01). There were no episodes of CMV viremia in either treatment group. BKV viremias were significantly more common in the rituximab recipients (9%) compared with placebo controls (0, p<0.01). No JCV reactivations were detected in this study, but among 6 rituximab and 2 placebo recipients who seroconverted for JCV during the study, only one rituximab recipient had detectable viremia. All infections were asymptomatic. ConclusionsFour doses of rituximab administered to individuals with early onset T1D decreased the incidence of asymptomatic EBV reactivations, as predicted by the rituximab-mediated elimination of memory B-cells, but increased the frequency of asymptomatic viremias caused by polyomaviruses.

Are we Close Enough to get rid of AIDS: Insights in to Impact of Human Immunodeficiency Virus (HIV) Infection Post Highly Active Antiretroviral Therapy (HAART) Era.

Human Immunodeficiency Virus (HIV) is a retrovirus belonging to the Lentivirus group that also consists of Simian Immunodeficiency Virus (SIV) that causes AIDS in monkeys and have the ability to cause chronic infections. Previous studies have confirmed the occurrence of opportunistic infections (OI's) with bacteria, fungi, parasites and viruses in HIV infected individuals when CD4T + cell counts fall below 200 cells/mm 3 . Studies have also highlighted the role of HIV infection in the development of carcinogenesis. Recently there have been many studies from around the globe establishing the role of HIV in the development of haematological, biochemical and metabolic disorders. Though a lot has improved in the laboratory diagnosis of HIV with the advent of newer generation detection methods, that considerably reduce window period, the cause of concern now is the effect of Highly Active Antiretroviral therapy (HAART), and the management of patients on HAART.

Pattern of HIV-1 Drug Resistance among Adults on ART in Nigeria

Background: The development of anitiretroviral drug resistance may limit the benefit of antiretroviral therapy. Therefore the need to closely monitor these mutations, especially the use of ART is increasing. This study was therefore designed to determine the ARV drug resistance pattern among ART na?ve and expose individuals attending a PEPFAR supported by antiretroviral clinic in Nigeria. Methodology: The study participants included patients attending the PEPFAR supported by University College Hospital (UCH), Ibadan ART clinic who have been on HIV treatment for at least one year with consecutive viral load of over 2000 copies/ml as well some ART Na?ve individuals with high (>50,000 copies/ml) baseline viral level attending the hospital for pre-ART assessment. Blood sample was collected from each individual for CD4 enumeration, viral load level determination and DNA sequencing for genotypic typing. Antiretroviral drug resistance mutations (DRM) were determined by using the Viroseq software and drug mutations generated by using a combination of Viroseq and Stanford algorithm. DRM were classified as major or minor mutations based on the June 2013 Stanford DR database. Results: The most common major NRTI, NNRTI and PI mutation were D67N (33.3%), Y181C (16.7%) and M46L/I (55.6%) respectively. Lamivudine (3TC) and emtricitabine (FTC); nevirapine (NVP) and nelfinavir (NFV) were the most common NRTI, NNRTI, and PI drugs to which the virus in the infected individuals developed resistance. Isolates from 4 patients were resistant to triple drug class, including at least one NRTI, NNRTI and a PI. Only one (4.8%) of the isolates from drug Na?ve individuals had major DRM that conferred resistance to any drug. Conclusion: Demonstration of high rates of antiretroviral DRM among patients on 1st and 2nd line ART and the presence of DRM in drug Na?ve individuals in this study show the importance of surveillance for resistance to ARV in line with the magnitude of scaling up of treatment program in the country.

Histone Deacetylase Inhibitor MC1293 Induces Latent HIV-1 Reactivation by Histone Modification In Vitro Latency Cell Lines

HIV-1 latency remains a major problem for the eradication of viruses in infected individuals. We evaluated the effect of MC1293 on the epigenetic change at HIV-1 LTR and the induction of the latent viruses in the latency Jurkat T cell line. We found MC1293 can activate HIV-1 gene expression, increase the acetylation level of H3 and H4 at the nuc-1 site of HIV-1 LTR. In addition, MC1293 can synergize with prostratin to activate the HIV-1 promoter, and has relatively lower toxicity compared to Trichostatin A (TSA). The results suggest that the acetylation of histone plays an important role in regulating HIV-1 LTR gene expression, and MC1293 is potential drug candidate for antilatency therapies.

English

Hepatitis C virus (HCV) continues to be a major disease burden affecting about 200 million people in world. Using blood donors as a prevalence source may underestimate the real prevalence of the virus because the donors are highly selected population. Presently more evidences support intravenous drug use as leading risk factor for the spread of virus. OBJECTIVES: The study aims at finding out the seroprevelance of Hepatitis C virus in high risk individuals as well as healthy blood donors. SETTINGS AND DESIGN: The study group comprise of 350 subjects which included 150 healthy voluntary donors as control group and 200 subjects taken from different high risk population like intravenous drug abuser (50), patients on long term haemodialysis (40), patients with chronic liver disease (50), HIV positive cases (30), health care workers (30). STATISTICAL ANALYSIS USED: Percentage. RESULTS: Seropositivity for anti HCV antibody was found to be 12% (24/200) among high risk population and 0.66 % (1/150) in healthy voluntary blood donors. Among different high risk groups, maximum prevalence rate 28% (14/50) was found in I.V drug abusers. Fifty percent (7/14) of the seropositive parenteral drug abusers were male in the age group of 21-30 years followed by 35.7% (5/14) in 31-40 years of age group. Only one female (7.14%) between 21-30 years was found to be sero-reactive for antiHCV antibody. In HIV co-infected cases 13.33 % (4/30) were seropositive for antiHCV antibody. In chronic liver disease (two hepatocellular carcinoma, one cirrhosis and one chronic hepatitis) and long standing haemodialysis, the prevalence rate for anti HCV was found to be 8% (4/50) and 5% (2/40) respectively. None of the health workers (0/30) found to be sero-reactive for antiHCV antibody. CONCLUSIONS: HCV poses a serious worldwide health problem affecting people from all walks of life in every country. In the present study 12% and 0.66% HCV prevalence was noticed in high risk group and healthy blood donors respectively. Among high risk group maximum prevalence (58.33%) was found in IV drug abusers. Prevention should target the reduction of virus transmission by health education, risk reduction counseling and thorough HCV screening following the suggestion of CDC, Atlanta, USA.

HIV infection

At a satellite meeting prior to the International AIDS Meeting in Washington DC in July, a great deal of discussion was focused on finding a “cure” for HIV infection [1]. While this objective has been discussed at various times over the past decade, the real incentive for this goal comes from the encouraging findings with Timothy Brown, also known as the “Berlin patient.” This HIV-infected man received hematopoietic stem cells from an HLA-matched donor whose genome naturally lacked CCR5, the major receptor for HIV. Five years after two transplants, Mr. Brown appears to be cured of HIV as well as leukemia [2]. Although potentially infected with both a virus that requires CCR5 for entry and a small population of viruses that can infect cells by another receptor, no infectious virus can be recovered from his blood and other tissues. This finding includes biopsies from the brain, bowel, and lymph nodes. Certainly his “cure” encourages approaches that could mimic this achievement in all HIV-infected individuals.

Effect of Histone Deacetylase Inhibitors on HIV Production in Latently Infected, Resting CD4+ T Cells From Infected Individuals Receiving Effective Antiretroviral Therapy

Persistence of the latent viral reservoir has been recognized as a major obstacle to eradicating human immunodeficiency virus (HIV) in infected individuals receiving antiretroviral therapy. It has been suggested that histone deacetylase inhibitors (HDACis) may purge HIV in the latent viral reservoir. However, the effect of HDACis on the degree and extent of HIV expression in the latent viral reservoir has not been fully delineated. Here we demonstrate that HDACis do not induce HIV production in the latent viral reservoir of aviremic individuals. Therefore, alternative therapeutic strategies may be necessary to eliminate HIV in the latent viral reservoir.

HIV reservoirs

Plasma HIV viremia can be suppressed and maintained below the limits of detection for prolonged periods of time in the vast majority of HIV-infected individuals who receive antiretroviral therapy (ART). Thus, the clinical outcome for HIV-infected individuals who have access to these drugs is dramatically improved. However, ART alone cannot eradicate HIV in infected individuals and this impediment is likely in part due to the persistence of viral reservoirs in the peripheral blood and lymphoid tissues of infected individuals despite the suppression of plasma viremia. In recent years, major research efforts have been dedicated to a better understanding of the pathogenesis of persistent HIV infection and to the development of therapeutic strategies aimed at eradicating virus in infected individuals receiving ART. In this review, we discuss the pathophysiology of CD4 T-cell HIV reservoirs, including recent advances in our understanding of the mechanisms of persistent viral infection and perspectives for eradication of HIV in infected individuals.

Exploring the Cause of Oseltamivir Resistance Against Mutant H274Y Neuraminidase by Molecular Simulation Approach

Oseltamivir (Tamiflu) is the preferred anti-viral drug employed to fight the flu virus in infected individuals. The principal target for this drug is a virus surface glycoprotein, neuraminidase (NA), which facilitates the release of nascent virus and thus spreads infections. Until recently, only a low prevalence of neuraminidase inhibitors (NAIs) resistance (<1%) had been detected in circulating viruses. However, there have been reports of significant numbers of A (H1N1) influenza strains with a H274Y neuraminidase mutation that was highly resistant to the NAI, oseltamivir. In this study, we highlight the effect of point mutation-induced oseltamivir resistance in H1N1 subtype neuraminidases by molecular docking and molecular dynamics simulation approach. Our results suggested that wild-type NA could be more indispensable for the oseltamivir binding, as characterized by minimum number of H-bonds, high flexibility and largest binding affinity than mutant-type NA. This study throws light on the possible effects of drug-resistant mutations on the large functionally important collective motions in biological systems.

Immune response to hepatitis B vaccination in HIV-positive adults with isolated antibodies to HBV core antigen

To investigate the merits of vaccination against hepatitis B virus (HBV) in HIV-positive individuals with isolated antibodies to hepatitis B core antigen (anti-HBc). HIV-positive patients with isolated anti-HBc and CD4 counts >200 cells/mm(3) received HBV vaccination. An antibody titre to hepatitis B surface antigen (anti-HBs titres) ≥10 IU/L one month post-vaccination was termed an anamnestic response; a titre <10 IU/L was termed a primary response. Patients with primary responses received a 3-dose vaccine course. Anti-HBs titres in all responders were measured 12 and 24 months post-vaccination. 37 patients were studied: 19 (51%) were co-infected with hepatitis C; median CD4 count was 443 cells/mm(3). 8/37 patients (22%) elicited an anamnestic response. 29/37 patients (78%) elicited a primary response. After a 3-dose vaccine course, 15/25 primary responders (60%) achieved anti-HBs titres ≥10 IU/L. HIV acquisition through injecting drug use was the only independent predictor of an anamnestic response (OR 22.9, CI 1.71-306.74, P=0.018). Median anti-HBs titres for anamnestic and primary responders were 51 IU/L (13-127) and 157 IU/L (25-650) respectively. Of all responders, 12/23 (52%) retained anti-HBs titres ≥10 IU/L at 24 months. Anti-HBs duration was not significantly different between anamnestic and primary responders. 23/37 HIV-positive patients (62%) with isolated anti-HBc achieved anti-HBs titres ≥10 IU/L after 1-3 vaccine doses. However, duration of this immune response was short-lived (<two years) in over half the responders. The implications regarding re-infection risk in this population are yet to be determined.

Central nervous system involvement in dengue

This study aimed to determine the frequency of CNS infection by dengue virus (DENV) in individuals with fatal outcomes. Samples of 150 individuals suspect of an infection disease and with fatal outcomes were investigated for evidence of the presence of DENV. The sampling was made up of 150 CSF, 120 tissue samples, and 109 blood specimens. The tests used were viral isolation, reverse transcriptase PCR, immunohistochemistry, nonstructural 1 antigen, and immunoglobulin M detection. Out of 150 studied patients, 84 were dengue positive. Evidence of the presence of DENV was found in 41 CSF, showing the following neurologic diagnosis: 46.3% encephalitis, 34.1% meningoencephalitis, and 19.5% meningitis, giving a frequency of 48.8% of the 84 dengue-positive cases. The major clinical manifestations observed on these individuals were fever, headache, mental irritability, breathless, vomiting, muscle pain, tiredness, abdominal pain, somnolence, restlessness, dizziness, cough, seizure, coma, and neck stiffness. Clinical manifestations and laboratory-positive results in CSF that may indicate the presence of DENV led to consider the invasion of CNS by DENV in these fatal cases studied, and showed that neurologic pathology was an important fatal complication in dengue cases.

Seroprevalence study of antibodies against influenza A(H1N1) 2009 virus after the second pandemic wave in Slovenia

The pandemic influenza (H1N1) 2009 virus, which combined genes from swine, human and avian influenza viruses, emerged in April 2009 and spread globally within the next month. The post-pandemic serological response to the influenza A(H1N1) 2009 virus in non-vaccinated individuals from the central part of Slovenia was studied. After the second pandemic wave, 226 serum samples from healthy preschool children, students, health care workers and blood donors not previously vaccinated with pandemic vaccine were investigated by use of microneutralization assays (MN). Data on previous vaccinations with seasonal influenza vaccine and recent acute respiratory infections were collected. The overall rate of seropositivity to the pandemic influenza virus was high: 76.9% of the participants had antibody titres of ≥20. A titre of ≥40 was detected in 54% of the serum samples tested, the highest prevalence being in the 15-17 age group. There was no statistically significant difference in MN titres between individuals who had never been vaccinated with influenza vaccine and those vaccinated at least once. History of ARI was not more frequent in subjects with MN titres ≥20, ≥40 or ≥80 (p-value 0.654, p-value 0.755 and p-value 1, respectively). High seroprevalence to pandemic influenza has been found in all age groups regardless of the absence of clinical picture compatible with acute respiratory infection. Previous vaccinations with seasonal influenza vaccines had no impact on serological response to the influenza A(H1N1) 2009 virus.

Evaluation of antibody frequency against HBV, HCV and HTLV-1.

This study was designed to evaluate the frequency of antibody against these viruses in individuals attending the endoscopy ward of Taleghani hospital Tehran, Iran. Blood-borne viruses such as hepatitis B and hepatitis C virus and HTLV-1 virus are among the world's public health problems. Hepatitis viruses cause liver problems and HTLV-1 infection can lead to adult T-Cell lymphoma (ATL). Blood samples of 219 individuals attending the endoscopy ward of Taleghani hospital between years 2009-2011 were collected. A questionnaire containing demographic data was completed for each subject. Blood samples were tested for antibody against HTLV-1, HCV and HBc by ELISA (Dia.pro Italy). In case of positive results for anti-HBc, samples were also tested for HBs Ag antigen. Ninety two subjects were male and 127 were female. Mean age of the population was 39.87 ± 16.47. None of the subjects had anti-HCV antibody, while 4 of them had anti-HTLV-1 antibody and 26 anti-HBc antibody; which only two of these individuals had HBs Antibody. The results of this study show that frequency of anti-HCV and anti-HTLV-1 antibodies are very low, while the frequency of anti-HBc was higher in the population. Since HTLV-1 is the causative agent of a type of blood cancer, it seems that screening of donated bloods in this region should be considered.

Molecular prevalence of JC virus in Tehran, Iran.

Since data about prevalence of JC virus in Iranian population is scarce, this study was designed to evaluate the prevalence of JC virus in healthy individuals who had attended Fajr hospital and Farjam clinical laboratory in Tehran, Iran. JC virus is the causative agent of progressive multifocal encephalopathy (PML) in individuals with suppressed immune system. There are some evidences that this virus is responsible for some forms of cancers for example colorectal and gastric cancers in humans. Urine samples from 133 healthy individuals older than 18 years old were collected and after extraction of viral DNA, PCR was performed to determine the presence of virus. Results of the test and demographic data of subjects were entered into SPSS program and were analyzed by it. 71 subjects were male and 62 individuals were female. Mean age of the population was 42.23 ± 13.47. From the total number of 133 subjects, 51 (38.3%) individuals were positive for the presence of JC virus. Gender had statistically significant relationship with JC virus presence (p= 0.042). Age was not significantly related to JC virus presence status (p= 0.3). Obtained rate of JC prevalence in this study is similar to the results of studies in India and Philippine. Because of this virus's role in AIDS and the role of this virus in gastrointestinal cancers have been revealed in recent years, the more extended studies on the prevalence of this virus in different populations in Iran is necessary.

Detection of human herpes viruses in patients with chronic and aggressive periodontitis and relationship between viruses and clinical parameters

Background and Aims:Recent microbiological researches have revealed the possible role of human cytomegalovirus (HCMV), Epstein barr virus (EBV), and herpes simplex virus (HSV-1 and HSV-2) in the etiopathogenesis of periodontal diseases. The present pilot study has been undertaken to detect the presence of these viruses in chronic periodontitis, aggressive periodontitis, and healthy individuals and to determine the relationship between these viruses and the clinical parameters.Materials and Methods:A total of 10 patients belonging to the age group of 18 to 55 years were included. The patients were randomly assigned into periodontally healthy (sulcus depth ≤ 3 mm), chronic periodontitis, and aggressive periodontitis with pockets measuring ≥6 mm. Seventy-five subgingival plaque samples (25 samples from each group) were collected and subjected to multiplex polymerase chain reaction for the detection of presence of HCMV, EBV, HSV-1, and HSV-2. The results were analyzed using one-way ANOVA for multiple group comparisons followed by Student's t-test for pair-wise comparisons. Categorical data was analyzed by Fisher's exact test.Results:HSV-1 was detected in 76% (P<0.001) of sites with chronic periodontitis and 80% (P<0.001) sites with aggressive periodontitis. EBV was detected in 32% (P<0.05) of sites with chronic periodontitis and aggressive periodontitis. The probing pocket depth and clinical attachment level was statistically significant in HSV-1 detected sites compared with undetected sites in aggressive periodontitis patientsConclusion:Among these viruses HSV-1 and EBV were found to be significantly associated with destructive periodontal disease, including chronic and aggressive periodontitis. Further, HSV-1 was found to be associated with severity and progression of destructive periodontal disease.

Epstein-Barr virus in healthy individuals from Portugal.

The Epstein-Barr virus (EBV) persists for long periods in latent state inside B-lymphocytes after primary infections, and reactivation usually occurs associated to immunosuppression conditions of the host. Recently, the detection of EBV DNA in circulation has been suggested as a predictor marker for the development of EBV related malignancies. The aim of our study was to characterize the frequency of circulating EBV in healthy individuals (n=508) from the North region of Portugal, using peripheral blood samples. Detection was performed by Nested-PCR which amplifies a fragment from the BamHIW region of the EBV genome. Our results revealed an overall frequency of 37.2% positive cases for EBV in circulation, with distinct distribution according to genre (39.7% in male individuals and 33.2% in females). We also found that EBV is more frequent in individuals with more than 56 years old compared to individuals with less than 56 years old (p=0.032; RR=1.41), mainly in the male group (p=0.024; OR=1.51). This is the first study which characterizes the frequency of EBV in circulation in healthy donors from the Northern Region of Portugal, revealing increased frequency of EBV in circulation in healthy individuals with differences depending on gender or age. Further studies are required to analyze the role of circulating EBV in the definition of susceptibilities to EBV associated diseases.

Brain Cell Reservoirs of Latent Virus in Presymptomatic HIV-Infected Individuals

We detected HIV-1 DNA in pure populations of perivascular macrophages, parenchymal microglia, and astrocytes, isolated using laser microdissection from brain tissue of five untreated individuals who died in the presymptomatic stage of infection from non-HIV causes. HIV-1 DNA was detected in the three cell populations, most consistently in perivascular macrophages, without evidence of productive infection. The percentage of PCR reactions detecting HIV-1 DNA in perivascular macrophages correlated inversely with peripheral blood CD4 counts. These findings demonstrate that brain cell reservoirs of latent HIV-1 exist before pathological HIV encephalitis and suggest that perivascular macrophage trafficking of latent virus into the brain increases with immunosuppression.