scholarly journals Genital Shedding of Human Immunodeficiency Virus Type-1 (HIV) When Antiretroviral Therapy Suppresses HIV Replication in the Plasma

2020 ◽  
Vol 222 (5) ◽  
pp. 777-786
Author(s):  
Marta Bull ◽  
Caroline Mitchell ◽  
Jaime Soria ◽  
Sheila Styrchak ◽  
Corey Williams ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Genetic Distances ◽  
Hiv Replication ◽  
Proliferating Cells ◽  
Limit Of Quantification ◽  
Hiv Rna ◽  
Dnase Treatment ◽  
Infected Cells ◽  
Genital Shedding ◽  
And Control

Abstract Background During antiretroviral treatment (ART) with plasma HIV RNA below the limit of quantification, HIV RNA can be detected in genital or rectal secretions, termed discordant shedding (DS). We hypothesized that proliferating cells produce virions without HIV replication. Methods ART-naive Peruvians initiating ART were observed for DS over 2 years. HIV env and pol genomes were amplified from DS. Antiretrovirals and cytokines/chemokines concentrations were compared at DS and control time points. Results Eighty-two participants had ART suppression. DS was detected in 24/82 (29%) participants: 13/253 (5%) cervicovaginal lavages, 20/322 (6%) seminal plasmas, and 6/85 (7%) rectal secretions. HIV RNA in DS specimens was near the limit of quantification and not reproducible. HIV DNA was detected in 6/13 (46%) DS cervicovaginal lavages at low levels. Following DNase treatment, 5/39 DS specimens yielded HIV sequences, all without increased genetic distances. Women with and without DS had similar plasma antiretroviral levels and DS in 1 woman was associated with inflammation. Conclusions HIV RNA and DNA sequences and therapeutic antiretroviral plasma levels did not support HIV replication as the cause of DS from the genital tract. Rather, our findings infer that HIV RNA is shed due to proliferation of infected cells with virion production.

scholarly journals Ongoing HIV Replication During ART Reconsidered

2017 ◽  
Vol 4 (3) ◽  
Author(s):  
Mary F Kearney ◽  
Ann Wiegand ◽  
Wei Shao ◽  
William R McManus ◽  
Michael J Bale ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Mononuclear Cells ◽  
Chain Reaction ◽  
Hiv Replication ◽  
Rna Sequences ◽  
Peripheral Blood Mononuclear ◽  
Plasma Virus ◽  
Hiv Rna ◽  
Blood Mononuclear Cells ◽  
Polymerase Chain

Abstract Lorenzo-Redondo et al. recently analyzed HIV RNA sequences in plasma virus and proviral DNA sequences in lymph nodes (LN) and peripheral blood mononuclear cells (PBMC) from samples collected over a 6-month period from 3 individuals following initiation of antiretroviral therapy (ART) and concluded that ongoing HIV replication occurred in LN despite ART and that this replication maintained the HIV reservoir. We analyzed the same sequences and found that the dataset was very limited (median of 5 unique RNA or DNA sequences per sample) after accounting for polymerase chain reaction resampling and hypermutation and that the few remaining DNA sequences after 3 and 6 months on ART were not more diverse or divergent from those in pre-ART in any of the individuals studied. These findings, and others, lead us to conclude that the claims of ongoing replication on ART made by Lorenzo-Redondo et al. are not justified from the dataset analyzed in their publication.

scholarly journals An Increasing Proportion of Monotypic HIV-1 DNA Sequences during Antiretroviral Treatment Suggests Proliferation of HIV-Infected Cells

2012 ◽  
Vol 87 (3) ◽  
pp. 1770-1778 ◽  
Author(s):  
Thor A. Wagner ◽  
Jen L. McKernan ◽  
Nicole H. Tobin ◽  
Ken A. Tapia ◽  
James I. Mullins ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Acute Infection ◽  
Bioinformatic Analysis ◽  
Genetic Distances ◽  
Relative Increase ◽  
Resistance Mutations ◽  
Calculated Concentration ◽  
Infected Cells ◽  
Hiv 1 ◽  
Over Time

ABSTRACTUnderstanding how HIV-1 persists during effective antiretroviral therapy (ART) should inform strategies to cure HIV-1 infection. We hypothesize that proliferation of HIV-1-infected cells contributes to persistence of HIV-1 infection during suppressive ART. This predicts that identical or monotypic HIV-1 DNA sequences will increase over time during ART. We analyzed 1,656envandpolsequences generated following single-genome amplification from the blood and sputum of six individuals during long-term suppressive ART. The median proportion of monotypic sequences increased from 25.0% prior to ART to 43.2% after a median of 9.8 years of suppressive ART. The proportion of monotypic sequences was estimated to increase 3.3% per year (95% confidence interval, 2.3 to 4.4%;P< 0.001). Drug resistance mutations were not more common in the monotypic sequences, arguing against viral replication during times with lower antiretroviral concentrations. Bioinformatic analysis found equivalent genetic distances of monotypic and nonmonotypic sequences from the predicted founder virus sequence, suggesting that the relative increase in monotypic variants over time is not due to selective survival of cells with viruses from the time of acute infection or from just prior to ART initiation. Furthermore, while the total HIV-1 DNA load decreased during ART, the calculated concentration of monotypic sequences was stable in children, despite growth over nearly a decade of observation, consistent with proliferation of infected CD4+T cells and slower decay of monotypic sequences. Our findings suggest that proliferation of cells with proviruses is a likely mechanism of HIV-1 DNA persistence, which should be considered when designing strategies to eradicate HIV-1 infection.

scholarly journals RNase L Inhibitor Is Induced during Human Immunodeficiency Virus Type 1 Infection and Down Regulates the 2-5A/RNase L Pathway in Human T Cells

1999 ◽  
Vol 73 (1) ◽  
pp. 290-296 ◽  
Author(s):  
Camille Martinand ◽  
Céline Montavon ◽  
Tamim Salehzada ◽  
Michelle Silhol ◽  
Bernard Lebleu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Rnase L ◽  
Hiv Replication ◽  
Hiv Rna ◽  
Rnase L Inhibitor ◽  
Immunodeficiency Virus ◽  
Infected Cells

ABSTRACT The interferon-regulated 2-5A/RNase L pathway plays a major role in the antiviral and antiproliferative activities of these cytokines. Several viruses, however, have evolved strategies to escape the antiviral activity of the 2-5A/RNase L pathway. In this context, we have cloned a cDNA coding for the RNase L inhibitor (RLI), a protein that specifically inhibits RNase L and whose regulated expression in picornavirus-infected cells down regulates the activity of the 2-5A/RNase L pathway. We show here that RLI increases during the course of human immunodeficiency virus type 1 (HIV-1) infection, which may be related to the downregulation of RNase L activity that has been described to occur in HIV-infected cells. In order to establish a possible causal relationship between these observations, we have stably transfected H9 cells with RLI sense or antisense cDNA-expressing vectors. The overexpression of RLI causes a decrease in RNase L activity and a twofold enhancement of HIV production. This increase in HIV replication correlates with an increase in HIV RNA and proteins. In contrast, reduction of RLI levels in RLI antisense cDNA-expressing clones reverses the inhibition of RNase L activity associated with HIV multiplication and leads to a threefold decrease in the viral load. This anti-HIV activity correlated with a decrease in HIV RNA and proteins. These findings demonstrate that the level of RLI, via its modulation of RNase L activity, can severely impair HIV replication and suggest the involvement of RLI in the inhibition of the 2-5A/RNase L system observed during HIV infection.

scholarly journals Productive Infection Maintains a Dynamic Steady State of Residual Viremia in Human Immunodeficiency Virus Type 1-Infected Persons Treated with Suppressive Antiretroviral Therapy for Five Years

2003 ◽  
Vol 77 (20) ◽  
pp. 11212-11219 ◽  
Author(s):  
Diane V. Havlir ◽  
Matthew C. Strain ◽  
Mario Clerici ◽  
Caroline Ignacio ◽  
Daria Trabattoni ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Productive Infection ◽  
Suppressive Therapy ◽  
Residual Viremia ◽  
Hiv Replication ◽  
Hiv Rna ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Rna Levels

ABSTRACT To provide insight into the dynamics and source of residual viremia in human immunodeficiency virus (HIV) patients successfully treated with antiretroviral therapy, 14 intensely monitored patients treated with indinavir and efavirenz sustaining HIV RNA at <50 copies/ml for >5 years were studied. Abacavir was added to the regimen of eight patients at year 5. After the first 9 months of therapy, HIV RNA levels had reached a plateau (“residual viremia”) that persisted for over 5 years. Levels of residual viremia differed among patients and ranged from 3.2 to 23 HIV RNA copies/ml. Baseline HIV DNA was the only significant pretreatment predictor of residual viremia in regression models including baseline HIV RNA, CD4 count, and patient age. In the four of five patients with detectable viremia who added abacavir to their regimen after 5 years, HIV RNA levels declined rapidly. The estimated half-life of infected cells was 6.7 days. Decrease in activated memory cells and a reduction in gamma interferon production to HIV Gag and p24 antigen in ELISpot assays were observed, consistent with a decrease in HIV replication. Thus, in patients treated with efavirenz plus indinavir, levels of residual viremia were established by 9 months, were predicted by baseline proviral DNA, and remained constant for 5 years. Even after years of highly suppressive therapy, HIV RNA levels declined rapidly after the addition of abacavir, suggesting that productive infection contributes to residual ongoing viremia and can be inhibited with therapy intensification.

Electron Microscopy of a Herpesvirus Isolated from Marek's Disease in Duck and Chicken Embryo Fibroblast Cultures

1968 ◽  
Vol 26 ◽  
pp. 222-223 ◽  
Author(s):  
Keyvan Nazerian
Keyword(s):  
Inclusion Bodies ◽  
Chicken Embryo Fibroblast ◽  
Marek's Disease ◽  
Marek’S Disease ◽  
Duck Embryo Fibroblast ◽  
Multinucleated Cells ◽  
Viral Particles ◽  
Infected Cells ◽  
And Control ◽  
Do So

A herpes-like virus has been isolated from duck embryo fibroblast (DEF) cultures inoculated with blood from Marek's disease (MD) infected birds. Cultures which contained this virus produced MD in susceptible chickens while virus negative cultures and control cultures failed to do so. This and other circumstantial evidence including similarities in properties of the virus and the MD agent implicate this virus in the etiology of MD.Histochemical studies demonstrated the presence of DNA-staining intranuclear inclusion bodies in polykarocytes in infected cultures. Distinct nucleo-plasmic aggregates were also seen in sections of similar multinucleated cells examined with the electron microscope. These aggregates are probably the same as the inclusion bodies seen with the light microscope. Naked viral particles were observed in the nucleus of infected cells within or on the edges of the nucleoplasmic aggregates. These particles measured 95-100mμ, in diameter and rarely escaped into the cytoplasm or nuclear vesicles by budding through the nuclear membrane (Fig. 1). The enveloped particles (Fig. 2) formed in this manner measured 150-170mμ in diameter and always had a densely stained nucleoid. The virus in supernatant fluids consisted of naked capsids with 162 hollow, cylindrical capsomeres (Fig. 3). Enveloped particles were not seen in such preparations.

Patiriella pseudoexigua (Asteroidea: Asterinidae): a cryptic species complex revealed by molecular and embryological analyses

2003 ◽  
Vol 83 (5) ◽  
pp. 1109-1116 ◽  
Author(s):  
Michael W. Hart ◽  
Maria Byrne ◽  
Sheri L. Johnson
Keyword(s):  
Dna Sequences ◽  
Original Description ◽  
Sensu Stricto ◽  
Genetic Distances ◽  
New Combination ◽  
Sea Stars ◽  
Planktonic Larva ◽  
Closely Related Species ◽  
Planktonic Larvae ◽  
Cryptic Species Complex

Cryptic lineages were identified within a morphologically uniform group of sea stars distributed from Australia to Japan. Among eight populations, all of which have been referred to Patiriella pseudoexigua, we found seven unique mitochondrial DNA sequences clustered into four distinct lineages. These four lineages formed a monophyletic group in which sister clades were separated by small genetic distances but could be differentiated from each other on the basis of reproductive differences. The four lineages thus appear to be separate but very closely related species. Examination of reproduction in several Queensland populations revealed that one population (Statue Bay) consisted of hermaphroditic intragonadal brooders with live-born offspring while other populations (Townsville, Bowen, Airlie Beach) consisted of dioecious free-spawners with a planktonic larva. The brooded larvae from central Queensland populations closely resembled brooded embryos and larvae of a Japanese lineage, while the planktonic larvae from northern Queensland were similar to the original description of planktonic larvae from a Taiwan population. However, each of the viviparous lineages was more closely related to a lineage with planktonic larval development than the viviparous lineages were to each other. Patiriella pseudoexigua thus comprises at least four species with different reproductive phenotypes in which viviparous brooding appears to have evolved in parallel. Based on previous taxonomic work we propose the following names for these four lineages: the dioecious free-spawner from northern Queensland (including the P. pseudoexigua type locality) is P. pseudoexiguasensu stricto; the viviparous brooder from central Queensland is undescribed and here referred to as Patiriella sp. nov; the dioecious free-spawner from Taiwan is temporarily referred to as Patiriella sp. (a senior name for this species may be P. pentagonus); and the hermaphrodite brooder from Japan should be raised to specific status and referred to by the new combination P. pacifica.

scholarly journals Leishmaniasis: Current Status of Vaccine Development

2001 ◽  
Vol 14 (2) ◽  
pp. 229-243 ◽  
Author(s):  
Emanuela Handman
Keyword(s):  
Dna Sequences ◽  
Vaccine Development ◽  
Development Program ◽  
Skin Lesions ◽  
Mononuclear Phagocytes ◽  
Control Measures ◽  
Host Susceptibility ◽  
Current Status ◽  
Dna Encoding ◽  
And Control

SUMMARY Leishmaniae are obligatory intracellular protozoa in mononuclear phagocytes. They cause a spectrum of diseases, ranging in severity from spontaneously healing skin lesions to fatal visceral disease. Worldwide, there are 2 million new cases each year and 1/10 of the world's population is at risk of infection. To date, there are no vaccines against leishmaniasis and control measures rely on chemotherapy to alleviate disease and on vector control to reduce transmission. However, a major vaccine development program aimed initially at cutaneous leishmaniasis is under way. Studies in animal models and humans are evaluating the potential of genetically modified live attenuated vaccines, as well as a variety of recombinant antigens or the DNA encoding them. The program also focuses on new adjuvants, including cytokines, and delivery systems to target the T helper type 1 immune responses required for the elimination of this intracellular organism. The availability, in the near future, of the DNA sequences of the human and Leishmania genomes will extend the vaccine program. New vaccine candidates such as parasite virulence factors will be identified. Host susceptibility genes will be mapped to allow the vaccine to be targeted to the population most in need of protection.

DNA barcoding of bats (Chiroptera) from the Colombian northern region

Mammalia ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Álvaro J. Benítez ◽  
Dina Ricardo-Caldera ◽  
María Atencia-Pineda ◽  
Jesús Ballesteros-Correa ◽  
Julio Chacón-Pacheco ◽  
...  
Keyword(s):  
Dna Barcoding ◽  
Species Identification ◽  
Dna Sequences ◽  
Genetic Distances ◽  
Northern Region ◽  
Coi Gene ◽  
Individual Species ◽  
Species Variation ◽  
Molossus Molossus ◽  
Artibeus Lituratus

Abstract Bats are mammals of great ecological and medical importance, which have associations with different pathogenic microorganisms. DNA barcoding is a tool that can expedite species identification using short DNA sequences. In this study, we assess the DNA barcoding methodology in bats from the Colombian Northern region, specifically in the Córdoba department. Cytochrome oxidase subunit I (COI) gene sequences of nine bat species were typified, and their comparison with other Neotropic samples revealed that this marker is suitable for individual species identification, with ranges of intra-species variation from 0.1 to 0.9%. Bat species clusters are well supported and differentiated, showing average genetic distances ranging from 3% between Artibeus lituratus and Artibeus planirostris, up to 27% between Carollia castanea and Molossus molossus. C. castanea and Glossophaga soricina show geographical structuring in the Neotropic. The findings reported in this study confirm DNA barcoding usefulness for fast species identification of bats in the region.

scholarly journals CXCR2 Blockade Influences Anaplasma phagocytophilum Propagation but Not Histopathology in the Mouse Model of Human Granulocytic Anaplasmosis

2004 ◽  
Vol 11 (5) ◽  
pp. 963-968 ◽  
Author(s):  
Diana G. Scorpio ◽  
Mustafa Akkoyunlu ◽  
Erol Fikrig ◽  
J. Stephen Dumler
Keyword(s):  
Anaplasma Phagocytophilum ◽  
Tissue Injury ◽  
Treated Group ◽  
Obligate Intracellular Bacterium ◽  
Human Granulocytic Anaplasmosis ◽  
Obligate Intracellular ◽  
Liver Histopathology ◽  
Granulocytic Anaplasmosis ◽  
Infected Cells ◽  
And Control

ABSTRACT Anaplasma phagocytophilum is an obligate intracellular bacterium that infects neutrophils and causes human granulocytic anaplasmosis. Infection induces neutrophil secretion of interleukin-8 or murine homologs and perpetuates infection by recruiting susceptible neutrophils. We hypothesized that antibody blockade of CXCR2 would decrease A. phagocytophilum tissue load by interrupting neutrophil recruitment but would not influence murine hepatic pathology. C3H-scid mice were treated with CXCR2 antiserum or control prior to or on day 14 after infection. Quantitative PCR and immunohistochemistry for A. phagocytophilum were performed and severity of liver histopathology was ranked. Control mice had more infected cells in tissues than the anti-CXCR2-treated group. The histopathological rank was not different between treated and control animals. Infected cells of control mice clustered in tissue more than in treated mice. The results support the hypothesis of bacterial propagation through chemokine induction and confirm that tissue injury is unrelated to A. phagocytophilum tissue load.

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