scholarly journals The Second Extracellular Loop of CXCR4 Determines Its Function as a Receptor for Feline Immunodeficiency Virus

1998 ◽  
Vol 72 (8) ◽  
pp. 6475-6481 ◽  
Author(s):  
Brian J. Willett ◽  
Karen Adema ◽  
Nikolaus Heveker ◽  
Anne Brelot ◽  
Laurent Picard ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Receptor Internalization ◽  
Receptor Function ◽  
Extracellular Loop ◽  
Critical Determinant ◽  
Susceptibility To Infection ◽  
Extracellular Loops ◽  
Immunodeficiency Virus ◽  
Dry Motif ◽  
Infected Cells

ABSTRACT The feline homolog of the α-chemokine receptor CXCR4 has recently been shown to support cell-cell fusion mediated by CXCR4-dependent strains of human immunodeficiency virus (HIV) and strains of feline immunodeficiency virus (FIV) that have been selected for growth in the Crandell feline kidney (CrFK) cell line. In this report we demonstrate that expression of CXCR4 alone is sufficient to render cells from diverse species permissive for fusion with FIV-infected cells, suggesting that CXCR4 is the sole receptor for CrFK-tropic strains of FIV, analogous to CD4-independent strains of HIV-2. To identify the regions of CXCR4 involved in fusion mediated by FIV, we screened panels of chimeric CXCR4 molecules for the ability to support fusion with FIV-infected cells. Human CXCR4 supported fusion more efficiently than feline CXCR4 and feline/human CXCR4 chimeras, suggesting that the second and third extracellular loops of human CXCR4 contain a critical determinant for receptor function. Rat/human CXCR4 chimeras suggested that the second extracellular loop contained the principal determinant for receptor function; however, chimeras constructed between human CXCR2 and CXCR4 revealed that the first and third loops of CXCR4 contribute to the FIV Env binding site, as replacement of these domains with the corresponding domains of CXCR2 rendered the molecule nonfunctional in fusion assays. Mutation of the DRY motif and the C-terminal cytoplasmic tail of CXCR4 did not affect the ability of the molecule to support fusion, suggesting that neither signalling via G proteins nor receptor internalization was required for fusion mediated by FIV; similarly, truncation of the N terminus of CXCR4 did not affect the function of the molecule as a receptor for FIV. CXCR4-transfected feline cells were rendered permissive for infection with both the CrFK-tropic PET isolate of FIV and the CXCR4-dependent RF strain of HIV-1, and susceptibility to infection correlated well with ability to support fusion. The data suggest that the second extracellular loop of CXCR4 is the major determinant of CXCR4 usage by FIV.

scholarly journals Identification of a Central DNA Flap in Feline Immunodeficiency Virus

2001 ◽  
Vol 75 (19) ◽  
pp. 9407-9414 ◽  
Author(s):  
Todd Whitwam ◽  
Mary Peretz ◽  
Eric Poeschla
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Strand Displacement ◽  
Preintegration Complex ◽  
S1 Nuclease ◽  
Guanine Residue ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Strand Initiation ◽  
Hiv 1

ABSTRACT A duplication of the polypurine tract (PPT) at the center of the human immunodeficiency virus type 1 (HIV-1) genome (the cPPT) has been shown to prime a separate plus-strand initiation and to result in a plus-strand displacement (DNA flap) that plays a role in nuclear import of the viral preintegration complex. Feline immunodeficiency virus (FIV) is a lentivirus that infects nondividing cells, causes progressive CD4+ T-cell depletion, and has been used as a substrate for lentiviral vectors. However, the PPT sequence is not duplicated elsewhere in the FIV genome and a central plus-strand initiation or strand displacement has not been identified. Using Southern blotting of S1 nuclease-digested FIV preintegration complexes isolated from infected cells, we detected a single-strand discontinuity at the approximate center of the reverse-transcribed genome. Primer extension analyses assigned the gap to the plus strand, and mapped the 5′ terminus of the downstream (D+) segment to a guanine residue in a purine-rich tract in pol(AAAAGAAGAGGTAGGA). RACE experiments then mapped the 3′ terminus of the upstream plus (U+)-strand segment to a T nucleotide located 88 nucleotides downstream of the D+ strand 5′ terminus, thereby identifying the extent of D+ strand displacement and the central termination sequence of this virus. Unlike HIV, the FIV cPPT is significantly divergent in sequence from its 3′ counterpart (AAAAAAGAAAAAAGGGTGG) and contains one and in some cases two pyrimidines. An invariant thymidine located −2 to the D+ strand origin is neither required nor optimal for codon usage at this position. Although the mapped cPPTs of FIV and HIV-1 act in cis, they encode homologous amino acids in integrase.

scholarly journals Early Pathogenesis of Transmucosal Feline Immunodeficiency Virus Infection

2002 ◽  
Vol 76 (12) ◽  
pp. 6311-6322 ◽  
Author(s):  
Leslie A. Obert ◽  
Edward A. Hoover
Keyword(s):  
Lymph Nodes ◽  
Feline Immunodeficiency Virus ◽  
Mononuclear Cells ◽  
Target Cells ◽  
Lymphoid Tissues ◽  
Vaginal Mucosa ◽  
Feline Immunodeficiency Virus Infection ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Dna Pcr

ABSTRACT To identify the early target cells and tissues in transmucosal feline immunodeficiency virus (FIV) infection, cats were exposed to a clade C FIV isolate via the oral-nasal or vaginal mucosa and multiple tissues were examined by virus isolation coculture (VI), DNA PCR, catalyzed tyramide signal-amplified in situ hybridization (TSA-ISH), and immunohistochemistry between days 1 and 12 postinoculation (p.i.). FIV RNA was detected in tonsil and oral or vaginal mucosa as early as 1 day p.i. by TSA-ISH and in retropharyngeal, tracheobronchial, or external iliac lymph nodes and sometimes in spleen or blood mononuclear cells by day 2, indicating that regional and distant spread of virus-infected cells occurred rapidly after mucosal exposure. By day 8, viral RNA, DNA, and culturable virus were uniformly detected in regional and distant tissues, connoting systemic infection. TSA-ISH proved more sensitive than DNA PCR in detecting early FIV-infected cells. In mucosal tissues, the earliest demonstrable FIV-bearing cells were either within or subjacent to the mucosal epithelium or were in germinal centers of regional lymph nodes. The FIV+ cells were of either of two morphological types, large stellate or small round. Those FIV RNA+ cells which could be colabeled for a phenotype marker, were labeled for either dendritic-cell-associated protein p55 or T-lymphocyte receptor antigen CD3. These studies indicate that FIV crosses mucous membranes within hours after exposure and rapidly traffics via dendritic and T cells to systemic lymphoid tissues, a pathway similar to that thought to occur in the initial phase of infection by the human and simian immunodeficiency viruses.

The Second Extracellular Loop of CXCR4 Determines Its Function as a Receptor for Feline Immunodeficiency Virus

1998 ◽  
Vol 72 (10) ◽  
pp. 8460-8460 ◽  
Author(s):  
Brian J. Willett ◽  
Karen Adema ◽  
Nikolaus Heveker ◽  
Anne Brelot ◽  
Laurent Picard ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Extracellular Loop ◽  
Immunodeficiency Virus

scholarly journals Differential Utilization of CD134 as a Functional Receptor by Diverse Strains of Feline Immunodeficiency Virus

2006 ◽  
Vol 80 (7) ◽  
pp. 3386-3394 ◽  
Author(s):  
Brian J. Willett ◽  
Elizabeth L. McMonagle ◽  
Susan Ridha ◽  
Margaret J. Hosie
Keyword(s):  
Amino Acids ◽  
Disease Progression ◽  
Feline Immunodeficiency Virus ◽  
Cell Tropism ◽  
Receptor Function ◽  
Rich Domain ◽  
Immunodeficiency Virus ◽  
Primary Determinant ◽  
Functional Receptor ◽  
Cysteine Rich Domain

ABSTRACT The feline homologue of CD134 (fCD134) is the primary binding receptor for feline immunodeficiency virus (FIV), targeting the virus preferentially to activated CD4+ helper T cells. However, with disease progression, the cell tropism of FIV broadens such that B cells and monocytes/macrophages become significant reservoirs of proviral DNA, suggesting that receptor utilization may alter with disease progression. We examined the receptor utilization of diverse strains of FIV and found that all strains tested utilized CD134 as the primary receptor. Using chimeric feline × human CD134 receptors, the primary determinant of receptor function was mapped to the first cysteine-rich domain (CRD1) of fCD134. For the PPR and B2542 strains, the replacement of CDR1 of fCD134 (amino acids 1 to 64) with human CD134 (hCD134) alone was sufficient to confer nearly optimal receptor function. However, evidence of differential utilization of CD134 was revealed, since strains GL8, CPGammer (CPG41), TM2, 0827, and NCSU1 required determinants in the region spanning amino acids 65 to 85, indicating that these strains may require a more stringent interaction for infection to proceed.

scholarly journals TNF-α-Induced Cell Death in Feline Immunodeficiency Virus-Infected Cells Is Mediated by the Caspase Cascade

Virology ◽  
2001 ◽  
Vol 287 (2) ◽  
pp. 446-455 ◽  
Author(s):  
Takuya Mizuno ◽  
Yuko Goto ◽  
Kenji Baba ◽  
Kenichi Masuda ◽  
Koichi Ohno ◽  
...  
Keyword(s):  
Cell Death ◽  
Feline Immunodeficiency Virus ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Caspase Cascade

Vaccination with fixed feline immunodeficiency virus (FIV) infected cells: protection, breakthrough and specificity of response

Vaccine ◽  
1996 ◽  
Vol 14 (13) ◽  
pp. 1243-1250 ◽  
Author(s):  
Sarah A. Bishop ◽  
Christopher R. Stokes ◽  
Timothy J. Gruffydd-Jones ◽  
Christine V. Whiting ◽  
James E. Humphries ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Immunodeficiency Virus ◽  
Infected Cells

scholarly journals An RNA-Directed Gene Editing Strategy for Attenuating the Infectious Potential of Feline Immunodeficiency Virus-Infected Cells: A Proof of Concept

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 511
Author(s):  
Brian G. Murphy ◽  
Tatiana Wolf ◽  
Helena Vogel ◽  
Diego Castillo ◽  
Kevin Woolard
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Gene Editing ◽  
Viral Transcription ◽  
Proof Of Concept ◽  
Antiviral Therapies ◽  
Immunodeficiency Virus ◽  
Patient Advocates ◽  
Infected Cells ◽  
Infectious Potential

Modern antiretroviral therapy for immunodeficiency viruses, although remarkably effective in controlling viral transcription, and overt virus-associated morbidity, has failed to absolutely eradicate retroviruses from their infected hosts as a result of proviral integration in long-lived reservoir cells. Immunodeficiency virus-infected patients are therefore consigned to lifelong antiviral therapy as a means to control viremia, viral transmission, and infection-associated morbidity. Unfortunately, lifelong antiviral therapies can be difficult for patients to continuously maintain and may be associated with therapy-specific morbidities. Patient advocates have argued for new methods to achieve retroviral eradication. As a proof-of-concept study, a lentivirus-delivered RNA-directed gene editing strategy was utilized in a series of in vitro experiments in an attempt to attenuate the feline immunodeficiency virus (FIV) proviral load, viral transcription, and production of infectious virions. We found that a feline T lymphocyte cell line (MCH5-4) treated with an FIV-specific clustered regularly interspersed short palindromic repeats (CRISPR)-associated protein 9 (Cas9) gene editing tool resulted in a reduction of cell-free viral RNA relative to control cells. Decreased infectious potential was demonstrated in a two-step FIV infection study—naïve MCH5-4 cells infected with cell-free FIV harvested from FIV-infected and CRISPR lentivirus-treated cells had less integrated proviral DNA than control cells. This study represents the initial steps towards the development of an effective method of proviral eradication in an immunodeficiency virus-infected host.

scholarly journals Vaccination against feline immunodeficiency virus using fixed infected cells

1995 ◽  
Vol 46 (1-2) ◽  
pp. 139-149 ◽  
Author(s):  
E.J. Verschoor ◽  
A.L.W. van Vliet ◽  
H.F. Egberink ◽  
W. Hesselink ◽  
W.E. van Alphen ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Immunodeficiency Virus ◽  
Infected Cells
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