Biomedical subjects

M A Rey-Cuille

Publications and source records attributed to M A Rey-Cuille.

4 recordsLinked to original sources

PubMed2001

Conserved CXCR4 usage and enhanced replicative capacity of HIV-2/287, an isolate highly pathogenic in Macaca nemestrina.

OBJECTIVE: To investigate viral properties that contribute to the pathogenic potential of HIV-2 in macaques. DESIGN: We compared HIV-2/287, a virus highly pathogenic in Macaca nemestrina, with its non-pathogenic progenitor HIV-2 EHO, for coreceptor usage and ability to infect human and macaque peripheral blood mononuclear cells (PBMC). METHODS: Coreceptor usage was determined in GHOST cells expressing known coreceptors, and in PBMC with coreceptor-specific inhibitors. Infectivity in PBMC was determined by virus titration and p27 antigen production. Early and late products of reverse transcription were measured by PCR with primers specific for the long terminal repeat (LTR), or the gag region, respectively. RESULTS: Both viruses preferentially infect HOS-CD4 cells expressing CXCR4. Inhibition by CXCR4-specific peptide TW70 and monoclonal antibody 12G5 indicated that both viruses use predominantly CXCR4 to infect macaque and human PBMC. HIV-2/287 showed greater infectivity than HIV-2 EHO in macaque cells, but the situation was reversed in human cells. Kinetic analysis of reverse transcription products revealed no restriction in reverse transcription following HIV-2 EHO infection of macaque PBMC. However, comparison of the level of newly initiated HIV-2 EHO DNA in macaque and human PBMC indicated that there is an early restriction, prior to the initiation of reverse transcription. CONCLUSIONS: Results indicate that the adaptation of HIV-2 EHO in M. nemestrina to a highly pathogenic virus HIV-2/287 is not correlated with a shift in or an expansion of coreceptor usage, but with the acquisition of an ability to overcome restrictions for growth in macaque PBMC.

Animals↗

PubMed2001

N-linked glycosylation in the V3 region of HIV type 1 surface antigen modulates coreceptor usage in viral infection.

The V3 hypervariable region of HIV-1 surface protein has been identified as a major determinant for viral tropism and coreceptor usage. However, the role of the highly conserved N-linked glycan at the V3 loop remains controversial. To further examine its role in viral infection, we introduced a conservative amino acid substitution (asparagine to glutamine) in the V3-proximal glycosylation motif (Asn-X-Ser/Thr) in the surface glycoprotein of a CXCR4-using virus (BRU), a CCR5-using virus (SF162), and a dual-tropic virus (89.6). The effect of the mutation was determined by complementation assays, and by infectivity on CEMx174 and U373-MAGI cells expressing either CXCR4 or CCR5. The mutation resulted in decreased CXCR4 usage by SHIV89.6, but increased usage by BRU. Similarly, it abrogated CCR5 usage by SHIV89.6, but had no effect on SF162. This effect was not dependent on the specific amino acid substitution used, because a threonine-toalanine mutation in the same motif in 89.6 Env yielded identical results as the asparagine-to-glutamine mutation. These findings support the notion that multiple factors, including glycosylation at V3, contribute to coreceptor usage and that the particular effects exerted by the N-linked glycan itself appear to be isolate dependent.

Amino Acid Motifs↗

PubMed2000

Derivation and characterization of a highly pathogenic isolate of human immunodeficiency virus type 2 that causes rapid CD4+ cell depletion in Macaca nemestrina.

With few exceptions, humans are the only species known to develop acquired immunodeficiency syndrome (AIDS) after human immunodeficiency virus (HIV) infection. We report here that an isolate of HIV type 2, EHO, readily established persistent infection in 100% of Macaca nemestrina in three consecutive transmission studies. Of the eight infected animals, five showed persistently high virus load and six developed AIDS-like diseases or CD4+ cell depletion within 4 years of infection. The pathology and clinical signs closely parallel those of HIV-1 infection of humans, including lymphadenopathy, anemia, CD4+ cell depletion, and opportunistic infections. A cell-free virus stock was established from the lymph nodes of an animal that developed AIDS-like diseases. This virus, HIV-2/287, was highly pathogenic in M. nemestrina, causing CD4+ cell depletion within 2-8 weeks postinfection. While both HIV-2 EHO and HIV-2/287 use predominantly CXCR4, the latter shows greatly enhanced replicative capacity in macaque peripheral blood mononuclear cells (PBMCs). The establishment of a human immunodeficiency virus that causes rapid and reproducible CD4 cell depletion in macaques could facilitate the study of HIV pathogenesis and the development of effective vaccines and therapy against AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1994

HIV-2 EHO isolate has a divergent envelope gene and induces single cell killing by apoptosis.

The human immunodeficiency virus type 2 (HIV-2)-related isolate, referred to as HIV-2 EHO, has been isolated from an Ivory Coast patient with acquired immunodeficiency syndrome (AIDS). Infection of CD4 expressing cells with this highly infectious virus mediates a cytopathic effect characterized by single-cell killing as a consequence of apoptosis. Nucleotide sequence analysis of the HIV-2 EHO genome revealed a significant degree of divergence of its envelope gene from that of other known HIV-2 strains. This divergence for the deduced amino acid sequence corresponding to the extracellular envelope glycoprotein was 26 to 30%. These unique genetic and biological properties suggest that the HIV-2 EHO isolate is a distinct prototype in the HIV-2 family.

Acquired Immunodeficiency Syndrome↗