HIV-1 Tropism: Truth or Consequences?

Tsai, Wen-Po; Kung, Hsiang‐Fu; Goudsmit, Jaap; Rimmelzwaan, Gustaaf; Minassian, A; Garrity, Robert R.; Nara, Peter L.

doi:10.1089/aid.1992.8.1749

Cited by 4 publications

(1 citation statement)

References 12 publications

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“…Recently, Layne et al demonstrated that the cell influences infection kinetics and physical properties generally attributed to the virus (34). In subsequent letters, Tsai et al (58) and Nara et al (41) have drawn on the evidence presented by Layne and others to highlight the often overlooked influence of the cell in experiments used to draw conclusions about viral tropism and susceptibility to inhibition. In contrast, Turner et al found no difference in susceptibility to soluble CD4 blocking when assays were carried out in parallel in PBMCs and the cell line C8166 (59).…”

Section: Discussionmentioning

confidence: 99%

Neutralization sensitivity of human immunodeficiency virus type 1 is determined in part by the cell in which the virus is propagated

Sawyer

Wrin

Crawford-Miksza

et al. 1994

J Virol

131

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Neutralizing antibody responses to human immunodeficiency virus type 1 (HIV-1) vary widely and have not been reproducibly associated with prognosis or disease progression. We have found that both low-passage clinical isolates and laboratory-adapted strains of HIV-1 have different sensitivities to neutralization by the same antiserum, depending on the host cell in which the viral stock is prepared. One such isolate (VL069) grown in H9 cells was neutralized by 20 human sera at a geometric mean titer of 1:2,047; this same isolate prepared in peripheral blood mononuclear cell (PBMC) culture was neutralized at a mean titer of < 1:10 by the same sera. Adsorption and mixing experiments indicated that neither antibody to H9 cell components nor blocking by excess viral antigen was responsible for the differences observed. This host cell effect is rapidly reversible upon passage of the virus from PBMCs to H9 cells and back into PBMCs. In contrast, the neutralization characteristics remained remarkably stable over extended culture in PBMCs. Two laboratory strains and five clinical isolates were evaluated in expanded studies of this phenomenon. While the neutralization characteristics of most of the strains studied were affected by the host cell in which the strain was propagated, two of the strains (one clinical isolate and one laboratory strain) appeared antigenically unaffected by their cell of origin. Host cell effect was also evident in neutralization by monoclonal antibodies directed against the CD4-binding region and the V2, V3, and gp41 regions. Possible mechanisms for this host cell effect include (i) mutation during passaging; (ii) selection in different host cells of different subpopulations of the (uncloned) viral stock; and (iii) cell-specific posttranslational modifications. To explore these possibilities, the V3 through V5 region of gp120 was sequenced in preparations made by passing VL069 into H9 cells and into PBMCs; HIVMN grown in CEM-SS cells and in PBMCs was also sequenced. In both cases, a few amino acid changes outside the V3 region were found. Studies are currently under way to assess the significance of these changes.

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Section: Discussionmentioning

confidence: 99%

Neutralization sensitivity of human immunodeficiency virus type 1 is determined in part by the cell in which the virus is propagated

Sawyer

Wrin

Crawford-Miksza

et al. 1994

J Virol

131

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Preliminary Findings of anin VitroHuman Spleen Mononuclear Cell Culture System for Primary Isolates of HIV Type 1

Tsai¹,

Rimelzwaan²,

Merges³

et al. 1997

AIDS Research and Human Retroviruses

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Acute HIV-1 infection is often manifested with a high level of viremia. The cell types and tissues/organs that contribute to the virus load are thought to be of central and peripheral lymphoreticular origin. The establishment and permissiveness of organ-based cell culture systems from spleen with laboratory strains or primary isolates of HIV-1 have not been reported. We studied unseparated splenic mononuclear cells (SMCs) and adherent cells derived from human spleen and liver in comparison with blood monocyte-derived macrophages (MDMs). Unstimulated, SMCs were highly permissive to primary lymphotropic HIV-1 and dual/macrophage-tropic isolates (which are able to replicate in both MDMs and PBMCs). Furthermore, SMCs were found to replicate virus to high titer in a rapid log-phase manner and exhibited a prolonged stationary phase of virus production, unlike PBMCs, which required conventional activation with mitogens and exhibited a much shorter period of virus production. Interestingly, the SMCs maintained themselves as a mixed phenotype of nested lymphocytes with complex and well-differentiated macrophage(s) for extended periods of time. In addition, splenic macrophages readily purified by adherence were highly permissive to a dual/macrophage-tropic primary isolate, HIV-1ADA, intermediate with two laboratory strains, HIVR-1RF and HIV-lHXB3, and least permissive to the lymphotropic primary isolate HIV-1Mr452 and two other laboratory strains, HIV-1CC and HIV-1MN. The replication of HIV-1ADA as measured by extracellular p24 was sustained for up to 7 weeks and similar to the replication patterns observed with adherent hepatic macrophages and blood-derived MDMs. This study demonstrates that exogenous stimulation is not required for infection of these cells; either adherence-isolated and/or mixed lymphoid populations can be studied together, and viable stocks can be readily prepared and cryopreserved. In addition, these cells could be used for isolating new and/or other variants of HIV-1. Thus, the use of the SMC primary in vitro cell culture system for future studies involving HIV-1 is warranted.

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HIV Receptors and the Pathogenesis of AIDS

Weiss

1996

Science

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There are many ways of approaching research on AIDS, and sometimes different philosophies clash. Robin Weiss (Chester Beatty Laboratories, Institute of Cancer Research, UK) wryly portrays the differences between the experimentalists and the theorists as they try to understand how the interactions of HIV and its human host result in disease. He also presents his view that recent discoveries of cofactors for HIV entry highlight the improtance of a cell biology—centered approach to understanding pathogenesis.

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HIV-1 Tropism: Truth or Consequences?

Cited by 4 publications

References 12 publications

Neutralization sensitivity of human immunodeficiency virus type 1 is determined in part by the cell in which the virus is propagated

Neutralization sensitivity of human immunodeficiency virus type 1 is determined in part by the cell in which the virus is propagated

Preliminary Findings of anin VitroHuman Spleen Mononuclear Cell Culture System for Primary Isolates of HIV Type 1

HIV Receptors and the Pathogenesis of AIDS

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