Longitudinal comparison of virus load parameters and CD8 T‐cell suppressive capacity in two SIVcpz‐infected chimpanzees

Ondoa, Pascale; Kestens, Luc; Davis, David A.; Vereecken, Chris; Willems, Betty; Fransen, Katrien; Vingerhoets, J.; Zissis, Georges; Haaft, Peter ten; Heeney, Jonathan L.; Groen, G van der

doi:10.1034/j.1600-0684.2001.d01-56.x

Cited by 16 publications

(34 citation statements)

References 45 publications

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“…What insight we do have, by necessity, has come from laboratory analyses of SIVcpz-infected captive chimpanzees and ex vivo analyses of their viruses and lymphoreticular tissues. For example, studies of several SIVcpz isolates indicate that, like HIV-1, they use CD4 and CCR5 as their main receptor and coreceptor for entry into target cells (10,50,58). For reasons that remain to be explained, it appears that chimpanzee peripheral blood mononuclear cells (PBMCs) are considerably less susceptible to SIVcpz (and HIV-1) infection in vitro than are human PBMCs (8,57).…”

Section: The Natural History Of Sivcpz Infectionmentioning

confidence: 99%

“…Even in captive chimpanzees, only seven naturally infected individuals have been identified (17,24,51,63,64), and among these, only one (Noah) has been subjected to virological and immunological analyses (13,40,41,54,(56)(57)(58). Observational studies of both captive and wildliving apes seem to suggest that SIVcpz-infected chimpanzees do not become noticeably immunodeficient or succumb prematurely to opportunistic infections or neoplasms, although an obvious caveat here is that it is difficult in field studies to distinguish between these and other natural causes of death.…”

Section: The Natural History Of Sivcpz Infectionmentioning

confidence: 99%

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Simian Immunodeficiency Virus Infection of Chimpanzees

Sharp

Shaw

Hahn³

2005

J Virol

179

135

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Simian immunodeficiency viruses (SIVs) are primate lentiviruses that infect no fewer than 36 different nonhuman primate species in sub-Saharan Africa (4,9,62). Two of these viruses, SIVcpz from chimpanzees (Pan troglodytes) and SIVsmm from sooty mangabeys (Cercocebus atys), have crossed species barriers on multiple occasions and have generated human immunodeficiency virus (HIV) types 1 and 2 (20,24,25,94). AIDS, one of the most devastating infectious diseases to have emerged in recent history, is thus the result of cross-species infections of humans by lentiviruses of primate origin (33).Identification of the primate source that spawned the HIV-1 pandemic is of scientific and public health importance. To this end, it is now well established that the immediate precursor of HIV-1 is a lentivirus that infects chimpanzees of the subspecies Pan troglodytes troglodytes in west central Africa (17,24). What is also known but perhaps less widely appreciated is that SIVcpz strains have been transmitted to humans on at least three independent occasions and that the current HIV-1 group M pandemic, which has afflicted more than 60 million people and caused more than 20 million deaths, resulted from just one of these transmission events in the first half of the twentieth century (42,77,97). The reasons for HIV-1's sudden emergence, the adaptive changes that followed, and the mechanisms underlying its unique pathogenicity in humans have not yet been determined.Primates naturally infected with SIV, including SIVcpz-infected chimpanzees, appear not to develop immunodeficiency or AIDS (31,40,49,60,70,79). In contrast, HIV infection of humans is nearly always characterized by progressive loss of CD4 ϩ T lymphocytes, chronic immune activation, and gradual destruction of an array of immune functions (82). The basis for this difference in pathogenicity is not understood, but deciphering which viral and/or host factors are responsible for the nonpathogenic course of natural SIV infections could well prove useful in developing more-effective treatment or prevention strategies for HIV/AIDS.Chimpanzees and humans share more than 98% sequence identity across their genomes (91). This degree of relatedness provides a unique opportunity to search for key differences in virus-host interactions responsible for differences in viral pathogenicity, an approach that could prove complementary to current studies that focus primarily on human disease susceptibility (55). In this review, we summarize recent progress in four key scientific areas related to AIDS pathogenesis: (i) the origin of HIV-1; (ii) the origin of SIVcpz; (iii) natural SIVcpz reservoirs; and (iv) the natural history of SIVcpz infection. Scientific and public health implications of these data as they relate to human infections by the corresponding virus, HIV-1, will also be discussed.

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Section: The Natural History Of Sivcpz Infectionmentioning

confidence: 99%

Section: The Natural History Of Sivcpz Infectionmentioning

confidence: 99%

Simian Immunodeficiency Virus Infection of Chimpanzees

Sharp

Shaw

Hahn³

2005

J Virol

179

135

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“…There are a few possible explanations to this puzzle. For example, chimps in the wild carry SIVcpz and show a low to moderate viral load yet appear to be immune to this lentivirus against the development of AIDS (Ondoa et al 2001). Similarly, several African non-human primates carry various versions of SIVs but remain unaffected by them.…”

Section: Role Of Sirnas In Development Of Hiv-1 Vaccinementioning

confidence: 99%

RNA interference: The molecular immune system

Bagasra

Prilliman²

2004

Histochem J

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SummaryIntroduction of double-stranded RNA (dsRNA) into cells expressing a homologous gene triggers RNA interference (RNAi), or RNA-based gene silencing (RBGS). The dsRNA degrades corresponding host mRNA into small interfering RNAs (siRNAs) by a protein complex containing Dicer. siRNAs in turn are incorporated into the RNA-induced silencing complex (RISC) that includes helicase, RecA, and exo-and endo-nucleases as well as other proteins. Following its assembly, the RISC guides the RNA degradation machinery to the target RNAs and cleaves the cognate target RNA in a sequence-specific, siRNA-dependent manner. RNAi has now been documented in a wide variety of organisms, including plants, fungi, flies, worms, and more recently, higher mammals. In eukaryotes, dsRNA directed against a range of viruses (i.e., HIV-1, RSV, HPV, poliovirus and others) and endogenous genes can induce sequence-specific inhibition of gene expression. In invertebrates, RNAi can be efficiently triggered by either long dsRNAs or 21-to 23-nt-long siRNAs. However, in jawed vertebrates, dsRNA longer than 30 bp can induce interferon and thus trigger undesirable side effects instead of initiating RNAi. siRNAs have been shown to act as potent inducers of RNAi in cultured mammalian cells. Many investigators have suggested that siRNAs may have evolved as a normal defense against endogenous and exogenous transposons and retroelements. Through a combination of genetic and biochemical approaches, some of the mechanisms underlying RNAi have been described. Recent data in C. elegans shows that two homologs of siRNAs, microRNAs (miRNAs) and tiny noncoding RNAs (tncRNAs) are endogenously expressed. However, many aspects of RNAi-induced gene silencing, including its origins and the selective pressures which maintain it, remain undefined. Its evolutionary history may pass through the more primitive immune functions of prokaryotes involving restriction enzymes that degrade plasmid DNA molecules that enter bacterial cells. RNAi has evolved further among eukaryotes, in which its wide distribution suggests early origins. RNAi seems to be involved in a variety of regulatory and immune functions that may differ among various kingdoms and phyla. We present here proposed mechanisms by which RBGS protects the host against endogenous and exogenous transposons and retroelements. The potential for therapeutic application of RBGS technology in treating viral infections such as HIV is also discussed.

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“…Previously, Kestens et al observed a fluctuating pattern with the measurement of virus titers in plasma varying from undetected to 1,000 tissue culture infectious doses/ml (49). From the end of 1997 to 2001 (i.e., dates after our panel), Ondoa et al quantified viral RNA from Ch-No plasma samples with a specific in-house assay, and the values varied from 3.93 to 5.80 log 10 copies/ml (50,51), in the range of our viral loads. Therefore, despite the high genetic distances between SIVcpz strains, our assay was able to detect and quantify the SIVcpzPtt and SIVcpzPts RNA from chimpanzee plasma samples.…”

Section: Reproducibility and Variations Between And Within Runsmentioning

confidence: 99%

Single Real-Time Reverse Transcription-PCR Assay for Detection and Quantification of Genetically Diverse HIV-1, SIVcpz, and SIVgor Strains

et al. 2013

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Although antiretroviral treatment availability has improved, the virological monitoring of patients remains largely uneven across regions. In addition, viral quantification tests are suffering from human immunodeficiency virus type 1 (HIV-1) genetic diversity, fueled by the emergence of new recombinants and of lentiviruses from nonhuman primates. We developed a real-time reverse transcription-PCR (RT-PCR) assay that is relatively inexpensive and able to detect and quantify all circulating forms of HIV-1 and its simian immunodeficiency virus (SIV) precursors, SIVcpz and SIVgor. Primers and a probe were designed to detect all variants of the HIV-1/SIVcpz/SIVgor lineage. HIV-1 M plasma (n ‫؍‬ 190; 1.68 to 7.78 log 10 copies/ml) representing eight subtypes, nine circulating recombinant forms, and 21 unique recombinant forms were tested. The mean PCR efficiency was 99%, with low coefficients of intra-and interassay variation (<5%) and a limit of quantification of <2.50 log 10 copies/ml, with a 200-l plasma volume. On the studied range, the specificity and the analytical sensitivity were 100 and 97.4%, respectively. The viral loads were highly correlated (r ‫؍‬ 0.95, P < 0.0001) with the reference method (generic HIV assay; Biocentric) and had no systematic difference, irrespective of genotype. Furthermore, 22 HIV-1 O plasmas were screened and were better quantified compared to the gold-standard RealTime HIV-1 assay (Abbott), including four samples that were only quantified by our assay. Finally, we could quantify SIVcpzPtt and SIVcpzPts from chimpanzee plasma (n ‫؍‬ 5) and amplify SIVcpz and SIVgor from feces. Thus, the newly developed real-time RT-PCR assay detects and quantifies strains from the HIV-1/SIVcpz/SIVgor lineage, including a wide diversity of group M strains and HIV-1 O. It can therefore be useful in geographical areas of high HIV diversity and at risk for the emergence of new HIV variants.

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Longitudinal comparison of virus load parameters and CD8 T‐cell suppressive capacity in two SIVcpz‐infected chimpanzees

Cited by 16 publications

References 45 publications

Simian Immunodeficiency Virus Infection of Chimpanzees

Simian Immunodeficiency Virus Infection of Chimpanzees

RNA interference: The molecular immune system

Single Real-Time Reverse Transcription-PCR Assay for Detection and Quantification of Genetically Diverse HIV-1, SIVcpz, and SIVgor Strains

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