Genomic Analysis of the Viral Population in Genital Secretions Early after Infection of Simian Immunodeficiency Viruses in Macaque Monkeys

Enose, Yoshimi; Ibuki, Kazuyasu; Shimada, Toshihide; Ui, Masahiro; Hayami, Masanori

doi:10.1111/j.1348-0421.1998.tb02344.x

Cited by 4 publications

(2 citation statements)

References 31 publications

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“…Our results are consistent with prior animal studies, in which macaques vaginally infected with a diverse simian immunodeficiency virus (SIV) population were found to have a reduced number of viral variants within weeks after inoculation, both in the plasma (25, 26) and in the vaginal tract (27). Given the challenge of capturing similarly early time points in human studies, our study represents the earliest examination of HIV-1 quasispecies in the human FGT, to our knowledge.…”

Section: Discussionsupporting

confidence: 92%

Metagenomic Sequencing of HIV-1 in the Blood and Female Genital Tract Reveals Little Quasispecies Diversity during Acute Infection

Piantadosi

Freije

Gosmann

et al. 2019

J Virol

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Due to error-prone replication, HIV-1 generates a diverse population of viruses within a chronically infected individual. When HIV-1 is transmitted to a new individual, one or a few viruses establish the new infection, leading to a genetic bottleneck in the virus population. Understanding the timing and nature of this bottleneck may provide insight into HIV-1 vaccine design and other preventative strategies. We examined the HIV-1 population in three women enrolled in a unique prospective cohort in South Africa who were followed closely during the earliest stages of HIV-1 infection. We found very little HIV-1 diversity in the blood and female genital tract during the first 2 weeks after virus was detected in the bloodstream. These results are compatible with a very early HIV-1 population bottleneck, suggesting the need to study the HIV-1 population in the female genital tract before virus is detectable in the bloodstream.

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Section: Discussionsupporting

confidence: 92%

Metagenomic Sequencing of HIV-1 in the Blood and Female Genital Tract Reveals Little Quasispecies Diversity during Acute Infection

Piantadosi

Freije

Gosmann

et al. 2019

J Virol

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show abstract

“…The model allows access to information that is usually unattainable in human studies, such as the genotypic and phenotypic properties of the infecting virus, knowledge of the exact time of virus exposure, and the characteristics of viral variants in the infected host immediately after transmission. Previous studies of SIV transmission using rhesus macaques inoculated by the IV and IVAG routes have shown that the genetic complexity of the SIV populations detected in peripheral blood is associated with the method of challenge; greater diversity accompanied IV inoculation of SIV (10,11,36,42). Some have concluded that these results mean that selective SIV transmission occurs after IVAG inoculation (11,36); however, a specific SIV variant has not been detected in multiple individual outbred macaques after IVAG inoculation with a genetically diverse virus stock.…”

Section: Human Immunodeficiency Virus (Hiv) Transmission By Sexual Imentioning

confidence: 65%

Route of Simian Immunodeficiency Virus Inoculation Determines the Complexity but Not the Identity of Viral Variant Populations That Infect Rhesus Macaques

Greenier

Miller

Ding

et al. 2001

J Virol

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A better understanding of the host and viral factors associated with human immunodeficiency virus (HIV) transmission is essential to developing effective strategies to curb the global HIV epidemic. Here we used the rhesus macaque-simian immunodeficiency virus (SIV) animal model of HIV infection to study the range of viral genotypes that are transmitted by different routes of inoculation and by different types of viral inocula. Analysis of transmitted variants was undertaken in outbred rhesus macaques inoculated intravenously (IV) or intravaginally (IVAG) with a genetically heterogeneous SIVmac251 stock derived from a well-characterized rhesus macaque viral isolate. In addition, we performed serial IV and IVAG passage experiments using plasma from SIV-infected macaques as the inoculum. We analyzed the V1-V2 region of the SIV envelope gene from virion-associated RNA in plasma from infected animals by the heteroduplex mobility assay (HMA) and by DNA sequence analysis. We found that a more diverse population of SIV genetic variants was present in the earliest virus-positive plasma samples from all five IV SIVmac251-inoculated monkeys and from two of five IVAG SIVmac251-inoculated monkeys. In contrast, we found a relatively homogeneous population of SIV envelope variants in three of five monkeys inoculated IVAG with SIVmac251 stock and in two monkeys infected after IVAG inoculation with plasma from an SIV-infected animal. In some IVAG-inoculated animals, the transmitted SIV variant was the most common variant in the inoculum. However, a specific viral variant in the SIVmac251 stock was not consistently transmitted by IVAG inoculation. Thus, it is likely that host factors or stochastic processes determine the specific viral variants that infect an animal after IVAG SIV exposure. In addition, our results clearly demonstrate that the route of inoculation is associated with the extent and breadth of the genetic complexity of the viral variant population in the earliest stages of systemic infection.

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Characterization of Less Pathogenic Infectious Molecular Clones Derived from Acute-Pathogenic SHIV-89.6P Stock Virus

et al. 2001

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For a better understanding of the acute pathogenicity of SHIV-89.6P stock virus, which induces prominent CD4 cell loss within a month after inoculation in monkeys, we have constructed four infectious molecular clones (cl 18, cl 64, cl 69, and cl 71). Cl 64, cl 69, and cl 71, like the parental virus, showed a high in vitro replication ability and a pathogenic-like effect (CD4 downmodulation) in a monkey CD4(+) cell line, whereas cl 18 showed a lower replication ability and could not downmodulate CD4. Cl 64, which has characteristics similar to those of the parental virus in vitro, was inoculated into four rhesus monkeys. All monkeys showed a plasma viral load similar to that of the parental virus with a peak at 2 weeks after inoculation. However, the viral load gradually decreased and the virus failed to cause an AIDS-like disease in infected monkeys, but it induced a strong antiviral antibody response. These results demonstrate the polyclonal nature of the parental SHIV-89.6P virus stock and demonstrate that cl 64, aside from its high replicability, may differ qualitatively from the parental virus.

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Genomic Analysis of the Viral Population in Genital Secretions Early after Infection of Simian Immunodeficiency Viruses in Macaque Monkeys

Cited by 4 publications

References 31 publications

Metagenomic Sequencing of HIV-1 in the Blood and Female Genital Tract Reveals Little Quasispecies Diversity during Acute Infection

Metagenomic Sequencing of HIV-1 in the Blood and Female Genital Tract Reveals Little Quasispecies Diversity during Acute Infection

Route of Simian Immunodeficiency Virus Inoculation Determines the Complexity but Not the Identity of Viral Variant Populations That Infect Rhesus Macaques

Characterization of Less Pathogenic Infectious Molecular Clones Derived from Acute-Pathogenic SHIV-89.6P Stock Virus

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