scholarly journals gp340 Promotes Transcytosis of Human Immunodeficiency Virus Type 1 in Genital Tract-Derived Cell Lines and Primary Endocervical Tissue

2009 ◽  
Vol 83 (17) ◽  
pp. 8596-8603 ◽  
Author(s):  
Earl Stoddard ◽  
Houping Ni ◽  
Georgetta Cannon ◽  
Chunhui Zhou ◽  
Neville Kallenbach ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Epithelial Cells ◽  
Cell Lines ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Genital Tract ◽  
Heterosexual Transmission ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The human scavenger receptor gp340 has been identified as a binding protein for the human immunodeficiency virus type 1 (HIV-1) envelope that is expressed on the cell surface of female genital tract epithelial cells. This interaction allows such epithelial cells to efficiently transmit infective virus to susceptible targets and maintain viral infectivity for several days. Within the context of vaginal transmission, HIV must first traverse a normally protective mucosa containing a cell barrier to reach the underlying T cells and dendritic cells, which propagate and spread the infection. The mechanism by which HIV-1 can bypass an otherwise healthy cellular barrier remains an important area of study. Here, we demonstrate that genital tract-derived cell lines and primary human endocervical tissue can support direct transcytosis of cell-free virus from the apical to basolateral surfaces. Further, this transport of virus can be blocked through the addition of antibodies or peptides that directly block the interaction of gp340 with the HIV-1 envelope, if added prior to viral pulsing on the apical side of the cell or tissue barrier. Our data support a role for the previously described heparan sulfate moieties in mediating this transcytosis but add gp340 as an important facilitator of HIV-1 transcytosis across genital tract tissue. This study demonstrates that HIV-1 actively traverses the protective barriers of the human genital tract and presents a second mechanism whereby gp340 can promote heterosexual transmission.

scholarly journals Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission

2019 ◽  
Vol 93 (13) ◽  
Author(s):  
Corey A. Williams-Wietzikoski ◽  
Mary S. Campbell ◽  
Rachel Payant ◽  
Airin Lam ◽  
Hong Zhao ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Genital Tract ◽  
Recent Common Ancestor ◽  
Female Partners ◽  
Immunodeficiency Virus ◽  
Male To Female ◽  
Hiv 1

ABSTRACTTo better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners. Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens collected near the time of transmission were studied. Single viral templates from blood plasma and genital tract RNA and DNA were sequenced across HIV-1envgp160. Eight of 29 couples examined yielded viral sequences from both tissues. Analysis of these couples’ sequences demonstrated, with one exception, that the women’s founding viral populations arose from a single viral variant and were CCR5 tropic, even though CXCR4 variants were detected within four males. The median genetic distance of the imputed most recent common ancestor of the women’s founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood. Using multiple assays, the blood and genital viruses were consistently found to be compartmentalized in only two of eight men. No distinct amino acid signatures in the men’s viruses were found to link to the women’s founders, nor did the women’senvsequences have shorter variable loops or fewer N-linked glycosylation sites. The lack of selective factors, except for coreceptor tropism, is consistent with others’ findings in male-to-female and high-risk transmissions. The infrequent compartmentalization between the transmitters’ blood and semen viruses suggests that cell-free blood virus likely includes HIV-1 sequences representative of those of viruses in semen.IMPORTANCEMucosal transmissions account for the majority of HIV-1 infections. Identification of the viral characteristics associated with transmission would facilitate vaccine design. This study of HIV strains from transmitting males and their seroconverting female partners found that the males’ genital tract viruses were rarely distinct from the blood variants. The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages. These findings suggest that targeting vaccine responses to variants found in blood are likely to also protect from genital tract variants.

scholarly journals A concurrent human herpesvirus-6 infection renders two human hematopoietic progenitor (TF-1 and KG-1) cell lines susceptible to human immunodeficiency virus type-1

Blood ◽  
1996 ◽  
Vol 87 (11) ◽  
pp. 4737-4745 ◽  
Author(s):  
G Furlini ◽  
M Vignoli ◽  
E Ramazzotti ◽  
MC Re ◽  
G Visani ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Lines ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Human Herpesvirus ◽  
Human Herpesvirus 6 ◽  
Hematopoietic Progenitors ◽  
Immunodeficiency Virus ◽  
Hiv 1

In human immunodeficiency virus type-1 (HIV-1) infected individuals, CD34+ hematopoietic stem/progenitor cells are profoundly impaired in their proliferation/differentiation capacities. The bulk of the available experimental evidence seems to indicate that hematopoietic progenitors are not susceptible to HIV-1 infection and their defects seem rather the consequence of direct or indirect negative influences of HIV-1-specific soluble proteins released by productively infected accessory cells. We have now shown that in the presence of a concurrent human herpesvirus-6 infection, two hematopoietic (TF-1 [erythromyeloid] and KG-1 [lymphomyeloid]) progenitor cell lines and human CD34+ hematopoietic progenitors isolated from the bone marrow of normal donors, became susceptible to HIV-1 infection and permissive to HIV-1 replication, although with a limited virus yield. These results suggest a further possible mechanism leading to hematopoietic derangement in HIV-1-infected subjects and may help to clarify the controversial issue of the susceptibility of human hematopoietic progenitors to HIV-1 infection.

scholarly journals The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells

2013 ◽  
Vol 9 (11) ◽  
pp. e1003776 ◽  
Author(s):  
Sandeep Gupta ◽  
Johannes S. Gach ◽  
Juan C. Becerra ◽  
Tran B. Phan ◽  
Jeffrey Pudney ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Epithelial Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Fc Receptor ◽  
Neonatal Fc Receptor ◽  
Immunodeficiency Virus ◽  
Hiv 1

Constitutive expression of the nef gene suppresses human immunodeficiency virus type 1 (HIV-1) replication in monocytic cell lines

Virology ◽  
1992 ◽  
Vol 191 (2) ◽  
pp. 960-963 ◽  
Author(s):  
Yasuko Tsunetsugu-Yokota ◽  
Shunji Matsuda ◽  
Midori Maekawat ◽  
Takashi Saito ◽  
Toshitada Takemori ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Lines ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Constitutive Expression ◽  
Monocytic Cell ◽  
Immunodeficiency Virus ◽  
Hiv 1

scholarly journals Human Immunodeficiency Virus Type 1 Env Sequences from Calcutta in Eastern India: Identification of Features That Distinguish Subtype C Sequences in India from Other Subtype C Sequences

2001 ◽  
Vol 75 (21) ◽  
pp. 10479-10487 ◽  
Author(s):  
Raj Shankarappa ◽  
Ramdas Chatterjee ◽  
Gerald H. Learn ◽  
Dhruba Neogi ◽  
Ming Ding ◽  
...  
Keyword(s):  
Amino Acids ◽  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Heterosexual Transmission ◽  
Subtype C ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT India is experiencing a rapid spread of human immunodeficiency virus type 1 (HIV-1), primarily through heterosexual transmission of subtype C viruses. To delineate the molecular features of HIV-1 circulating in India, we sequenced the V3-V4 region of viralenv from 21 individuals attending an HIV clinic in Calcutta, the most populous city in the eastern part of the country, and analyzed these and the other Indian sequences in the HIV database. Twenty individuals were infected with viruses having a subtype Cenv, and one had viruses with a subtype Aenv. Analyses of 192 subtype C sequences that included one sequence for each subject from this study and from the HIV database revealed that almost all sequences from India, along with a small number from other countries, form a phylogenetically distinct lineage within subtype C, which we designate CIN. Overall, CIN lineage sequences were more closely related to each other (level of diversity, 10.2%) than to subtype C sequences from Botswana, Burundi, South Africa, Tanzania, and Zimbabwe (range, 15.3 to 20.7%). Of the three positions identified as signature amino acid substitution sites for CIN sequences (K340E, K350A, and G429E), 56% of the CIN sequences contained all three amino acids while 87% of the sequences contained at least two of these substitutions. Among the non-CINsequences, all three amino acids were present in 2%, while 22% contained two or more of these amino acids. These results suggest that much of the current Indian epidemic is descended from a single introduction into the country. Identification of conserved signature amino acid positions could assist epidemiologic tracking and has implications for the development of a vaccine against subtype C HIV-1 in India.

scholarly journals Naturally processed viral peptides recognized by cytotoxic T lymphocytes on cells chronically infected by human immunodeficiency virus type 1.

1994 ◽  
Vol 180 (4) ◽  
pp. 1283-1293 ◽  
Author(s):  
T J Tsomides ◽  
A Aldovini ◽  
R P Johnson ◽  
B D Walker ◽  
R A Young ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Lymphocytes ◽  
Cell Lines ◽  
Cytotoxic T Lymphocytes ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

We have established long-term cultures of several cell lines stably and uniformly expressing human immunodeficiency virus type 1 (HIV-1) in order to (a) identify naturally processed HIV-1 peptides recognized by cytotoxic T lymphocytes (CTL) from HIV-1-seropositive individuals and (b) consider the hypothesis that naturally occurring epitope densities on HIV-infected cells may limit their lysis by CTL. Each of two A2-restricted CD8+ CTL specific for HIV-1 gag or reverse transcriptase (RT) recognized a single naturally processed HIV-1 peptide in trifluoroacetic acid (TFA) extracts of infected cells: gag 77-85 (SLYNTVATL) or RT 476-484 (ILKEPVHGV). Both processed peptides match the synthetic peptides that are optimally active in cytotoxicity assays and have the consensus motif described for A2-associated peptides. Their abundances were approximately 400 and approximately 12 molecules per infected Jurkat-A2 cell, respectively. Other synthetic HIV-1 peptides active at subnanomolar concentrations were not present in infected cells. Except for the antigen processing mutant line T2, HIV-infected HLA-A2+ cell lines were specifically lysed by both A2-restricted CTL, although infected Jurkat-A2 cells were lysed more poorly by RT-specific CTL than by gag-specific CTL, suggesting that low cell surface density of a natural peptide may limit the effectiveness of some HIV-specific CTL despite their vigorous activity against synthetic peptide-treated target cells.

scholarly journals Fluorescence-Based Quantitative Methods for Detecting Human Immunodeficiency Virus Type 1-Induced Syncytia

2000 ◽  
Vol 38 (8) ◽  
pp. 3055-3060 ◽  
Author(s):  
Sabina Wünschmann ◽  
Jack T. Stapleton
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Fusion ◽  
Cell Lines ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Quantitative Methods ◽  
Cytoplasmic Staining ◽  
Immunodeficiency Virus ◽  
Hiv 1

Cell fusion induced by human immunodeficiency virus type 1 (HIV-1) is usually assessed by counting multinucleated giant cells (syncytia) visualized by light microscopy. Currently used methods do not allow quantification of syncytia, nor do they estimate the number of cells involved in cell fusion. We describe two fluorescence-based methods for the detection and quantification of HIV-1-induced in vitro syncytium formation. The lymphoblastoid cell lines MT-2 and SupT1 were infected with syncytium-inducing (SI) HIV-1 isolates. Syncytia were detected by DNA staining with propidium iodide using flow cytometry to determine cell size or by two-color cytoplasmic staining of infected cell populations by using fluorescence microscopy. Both methods were able to detect and quantify HIV-induced syncytia. The methods could distinguish between SI and non-SI HIV isolates and could be used with at least two separate types of CD4+ T-cell lines. Small syncytia can be readily identified by the two-color cytoplasmic staining method. Both methods were also shown to be useful for evaluating antiretroviral compounds, as demonstrated by the accurate assessment of HIV inhibition by azidothymidine (zidovudine), dideoxycytidine (zalcytibine), and hydroxyurea. These fluorescence-based assays allow a rapid and practical method for measuring HIV replication and anti-HIV activity of potential inhibitory compounds.

scholarly journals Lack of negative influence on the cellular transcription factors NF-κB and AP-1 by the Nef protein of human immunodeficiency virus type 1

1999 ◽  
Vol 80 (11) ◽  
pp. 2951-2956 ◽  
Author(s):  
Keejung Yoon ◽  
Sunyoung Kim
Keyword(s):  
Human Immunodeficiency Virus ◽  
Transcription Factors ◽  
Cell Lines ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Negative Effect ◽  
Cellular Transcription ◽  
Hiv 1

In order to investigate the molecular mechanism of the reported negative effect of the Nef protein of human immunodeficiency virus type 1 (HIV-1) on the cellular transcription factors NF-κB and AP-1, human T cell lines (both populations and subclones) expressing the nef gene from HIV-1 clone pNL432 were constructed. Functional expression of the nef gene was confirmed by downregulation of CD4 and MHC class I proteins on the cell surface as measured by fluorescence-activated cell sorter analysis. However, contrary to previous reports, no significant difference was found in the induced level of NF-κB and AP-1 activity between nef + and nef − cell lines upon stimulation by phorbol 12-myristate 13-acetate and phytohaemagglutinin, as measured by transient transfection and electromobility shift assays. These data indicate that the Nef protein does not have a negative effect on the induction of NF-κB and AP-1.

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