In vivo replication capacity rather than in vitro macrophage tropism predicts efficiency of vaginal transmission of simian immunodeficiency virus or simian/human immunodeficiency virus in rhesus macaques - PubMed (original) (raw)

In vivo replication capacity rather than in vitro macrophage tropism predicts efficiency of vaginal transmission of simian immunodeficiency virus or simian/human immunodeficiency virus in rhesus macaques

C J Miller et al. J Virol. 1998 Apr.

Erratum in

Abstract

We used the rhesus macaque model of heterosexual human immunodeficiency virus (HIV) transmission to test the hypothesis that in vitro measures of macrophage tropism predict the ability of a primate lentivirus to initiate a systemic infection after intravaginal inoculation. A single atraumatic intravaginal inoculation with a T-cell-tropic molecular clone of simian immunodeficiency virus (SIV), SIVmac239, or a dualtropic recombinant molecular clone of SIV, SIVmac239/1A11/239, or uncloned dualtropic SIVmac251 or uncloned dualtropic simian/human immunodeficiency virus (SHIV) 89.6-PD produced systemic infection in all rhesus macaques tested. However, vaginal inoculation with a dualtropic molecular clone of SIV, SIVmac1A11, resulted in transient viremia in one of two rhesus macaques. It has previously been shown that 12 intravaginal inoculations with SIVmac1A11 resulted in infection of one of five rhesus macaques (M. L. Marthas, C. J. Miller, S. Sutjipto, J. Higgins, J. Torten, B. L. Lohman, R. E. Unger, H. Kiyono, J. R. McGhee, P. A. Marx, and N. C. Pedersen, J. Med. Primatol. 21:99-107, 1992). In addition, SHIV HXBc2, which replicates in monkey macrophages, does not infect rhesus macaques following multiple vaginal inoculations, while T-cell-tropic SHIV 89.6 does (Y. Lu, P. B. Brosio, M. Lafaile, J. Li, R. G. Collman, J. Sodroski, and C. J. Miller, J. Virol. 70:3045-3050, 1996). These results demonstrate that in vitro measures of macrophage tropism do not predict if a SIV or SHIV will produce systemic infection after intravaginal inoculation of rhesus macaques. However, we did find that the level to which these viruses replicate in vivo after intravenous inoculation predicts the outcome of intravaginal inoculation with each virus.

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Figures

FIG. 1

FIG. 1

In vitro replication of SIV and SHIV molecular clones in rhesus macaque monocyte-derived macrophages. The results shown here are representative of three separate experiments using monocyte-derived macrophages isolated from three rhesus macaques. (A) Replication of SIV molecular clones and uncloned SIVmac251. Note that SIVmac1A11, SIVmac239/1A11/239, and SIVmac251 replicate well in rhesus macaque macrophages. (B) Replication of SHIV molecular clones and uncloned SHIV 89.6-PD. Note that only SHIV HXBc2 and SHIV 89.6-PD replicate in rhesus macaque macrophages.

FIG. 2

FIG. 2

In vivo replication capacities of SIV molecular clones in rhesus macaques following i.v. inoculation. Three groups of animals (two animals per group) were inoculated i.v. with one of the three SIV molecular clones. The results of the analysis shown for each group of animals are arranged in columns, and the virus used to inoculate the animals in each group is noted at the top of each column. The rows are the data from a single assay: plasma p27 level (A), titer of infectious virus in plasma (B), cell-associated virus titer (C), viral RNA in plasma as measured by RT-QC-PCR (D), and viral RNA in plasma as measured by bDNA (E). Note that by all measures SIVmac239 has the highest replicative capacity, SIVmac1A11 has the lowest replicative capacity, and SIVmac239/1A11/239 has an intermediate replicative capacity. The most distinctive difference among the three SIV clones is that, unlike SIVmac239 and SIVmac239/1A11/239, i.v. inoculation with SIVmac1A11 did not result in sufficient virus replication to produce plasma antigenemia or infectious virus in plasma.

FIG. 3

FIG. 3

Viral p27 antigen in plasma of rhesus macaques inoculated with SHIV 89.6-PD. Plasma collected at the time points shown was tested for the presence of SIV p27 with a commercial antigen capture kit (Coulter Immunology). (A) Results for two animals i.v. inoculated with 25,000 TCID50 of SHIV 89.6-PD. Note that for both animals, the peak antigenemia occurs at 7 days p.i. (B) Results for five animals intravaginally inoculated with 25,000 TCID50 of SHIV 89.6-PD. Animal 25722 was negative in plasma p27 and virus isolation assays and is not included in the graph. Note that for the five infected animals, the peak plasma antigenemia occurs at 14 days p.i. Thus, the detection of viral antigen in the plasma of intravaginally inoculated animals was delayed by 7 days compared to that of the i.v. inoculated animals.

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