Enhanced replication of HIV‐1 <i>in vivo</i> in pigtailed macaques (<i>Macaca nemestrina</i>)

Bosch, Marnix L.; Schmidt, Ann Marie; Chen, Jiangli; Florey, Mary Jo; Agy, Michael B.; Morton, William R.

doi:10.1034/j.1600-0684.2000.290303.x

Cited by 15 publications

(16 citation statements)

References 11 publications

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“…We found that in comparison to RM, PTM progress more rapidly to AIDS-defining illnesses after SIVmac239 infection, but this accelerated rate of disease progression was not attributed to increased peak or set-point plasma viral loads. This is of interest, as previous studies have demonstrated that SHIV, HIV-1, and HIV-2 replicate at extremely high levels in pigtail macaques (3,6,24,42,49), and SIVagm replicates at variable levels (20). However, somewhat lower SIVmac239 replication rates followed by progression to AIDS are consistent with the immunodeficiency that is observed in PTM after infection with SIVsun or SIVhoest, where animals progress to AIDS despite low levels of viremia (4).…”

Section: Discussionmentioning

confidence: 49%

“…Importantly, in contrast to other nonhuman primate models, PTM are susceptible to many lentiviral infections other than SIV and SHIV, including infection with HIV-1, HIV-2, and simian tropic (stHIV-1) (1,3,6,24,29,42,49,55,60), which makes this model invaluable for vaccination and pathogenesis studies. Furthermore, recent characterization of APOBEC and TRIM5␣ genes in PTM has allowed for the development of minimally chimeric stHIV-1 strains, differing from HIV-1 only in vif genes, that persistently infect PTM due to the TRIMCyp fusion protein which PTM harbor rather than TRIM5 (11,21,60).…”

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confidence: 99%

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Dynamics of Simian Immunodeficiency Virus SIVmac239 Infection in Pigtail Macaques

Klatt

Canary

Vanderford

et al. 2012

J Virol

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Pigtail macaques (PTM) are an excellent model for HIV research; however, the dynamics of simian immunodeficiency virus (SIV) SIVmac239 infection in PTM have not been fully evaluated. We studied nine PTM prior to infection, during acute and chronic SIVmac239 infections, until progression to AIDS. We found PTM manifest clinical AIDS more rapidly than rhesus macaques (RM), as AIDS-defining events occurred at an average of 42.17 weeks after infection in PTM compared to 69.56 weeks in RM (P ‫؍‬ 0.0018). However, increased SIV progression was not associated with increased viremia, as both peak and set-point plasma viremias were similar between PTM and RM (P ‫؍‬ 0.7953 and P ‫؍‬ 0.1006, respectively). Moreover, this increased disease progression was not associated with rapid CD4 ؉ T cell depletion, as CD4 ؉ T cell decline resembled other SIV/human immunodeficiency virus (HIV) models. Since immune activation is the best predictor of disease progression during HIV infection, we analyzed immune activation by turnover of T cells by BrdU decay and Ki67 expression. We found increased levels of turnover prior to SIV infection of PTM compared to that observed with RM, which may contribute to their increased disease progression rate. These data evaluate the kinetics of SIVmac239-induced disease progression and highlight PTM as a model for HIV infection and the importance of immune activation in SIV disease progression.

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Section: Discussionmentioning

confidence: 49%

mentioning

confidence: 99%

Dynamics of Simian Immunodeficiency Virus SIVmac239 Infection in Pigtail Macaques

Klatt

Canary

Vanderford

et al. 2012

J Virol

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“…Based on their geographical distribution and morphology differences, pig-tailed macaques are divided into three species: sunda pig-tailed macaque ( M. nemestrina ), northern pig-tailed macaque ( M. leonina ), and mentawai macaque ( M. pagensis ) (8). The sunda pig-tailed macaques (SPMs) are the most frequently used species for HIV-1 infection (9–18). …”

Section: Introductionmentioning

confidence: 99%

Host Restriction Factors APOBEC3G/3F and Other Interferon-Related Gene Expressions Affect Early HIV-1 Infection in Northern Pig-Tailed Macaque (Macaca leonina)

Pang

Song

et al. 2018

Front. Immunol.

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The northern pig-tailed macaques (NPMs) lack TRIM5α, an antiviral restriction factor, and instead have TRIM5-CypA. In our previous study, we demonstrated that HIV-1NL4−3 successfully infected NPMs and formed a long-term viral reservoir in vivo. However, the HIV-1-infected NPMs showed relatively high viremia in the first 6 weeks of infection, which declined thereafter suggesting that HIV-1 NL4−3 infection in these animals was only partly permissive. To optimize HIV-1 infection in NPMs therefore, we generated HIV-1NL4−R3A and stHIV-1sv, and infected NPMs with these viruses. HIV-1NL4−R3A and stHIV-1sv can replicate persistently in NPMs during 41 weeks of acute infection stage. Compared to the HIV-1NL4−R3A, stHIV-1sv showed a notably higher level of replication, and the NPMs infected with the latter induced a more robust neutralizing antibody but a weaker cellular immune response. In addition, IFN-I signaling was significantly up-regulated with the viral replication, and was higher in the stHIV-1sv infected macaques. Consequently, the sequences of pro-viral env showed fewer G-A hyper-mutations in stHIV-1sv, suggesting that vif gene of SIV could antagonize the antiviral effects of APOBEC3 proteins in NPMs. Taken together, NPMs infected with HIV-1NL4−R3A and stHIV-1sv show distinct virological and immunological features. Furthermore, interferon-related gene expression might play a role in controlling primary HIV-1NL4−R3A and stHIV-1sv replication in NPMs. This result suggests NPM is a potential HIV/AIDS animal model.

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“…M. nemestrina macaques have also been reported to be susceptible to some HIV-1 isolates (1,(4)(5)(6)(7)19) although this idea remains controversial. These observations led us to examine the TRIM5 gene of M. nemestrina for species-specific differences that may explain the apparent susceptibility of this macaque species to infection with HIV.…”

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Novel TRIM5 Isoforms Expressed byMacaca nemestrina

Brennan

Kozyrev

Kodama

et al. 2007

J Virol

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The TRIM5 family of proteins contains a RING domain, one or two B boxes, and a coiled-coil domain. The TRIM5␣ isoform also encodes a C-terminal B30.2(SPRY) domain, differences within which define the breadth and potency of TRIM5␣-mediated retroviral restriction. Because Macaca nemestrina animals are susceptible to some human immunodeficiency virus (HIV) isolates, we sought to determine if differences exist in the TRIM5 gene and transcripts of these animals. We identified a two-nucleotide deletion (⌬2) in the transcript at the 5 terminus of exon 7 in all M. nemestrina TRIM5 cDNA clones examined. This frameshift results in a truncated protein of 300 amino acids lacking the B30.2(SPRY) domain, which we have named TRIM5. This deletion is likely due to a single nucleotide polymorphism that alters the 3 splice site between intron 6 and exon 7. In some clones, a deletion of the entire 27-nucleotide exon 7 (⌬exon7) resulted in the restoration of the TRIM5 open reading frame and the generation of another novel isoform, TRIM5. There are 18 amino acid differences between M. nemestrina TRIM5 and Macaca mulatta TRIM5␣, some of which are at or near locations previously shown to affect the breadth and potency of TRIM5␣-mediated restriction. Infectivity assays performed on permissive CrFK cells stably transduced with TRIM5 or TRIM5 show that these isoforms are incapable of restricting either HIV type 1 (HIV-1) or simian immunodeficiency virus infection. The expression of TRIM5 alleles incapable of restricting HIV-1 infection may contribute to the previously reported increased susceptibility of M. nemestrina to HIV-1 infection in vivo. The human immunodeficiency virus (HIV) pandemic is the result of cross-species transmissions of simian immunodeficiency virus (SIV) from non-human primates to humans (28).The recent discovery of human T-cell leukemia virus types 3 and 4 suggests that cross-species transmission of retroviruses is not an infrequent occurrence (33). However, to establish a productive infection in a new species, it is necessary for retroviruses to evade host-specific restriction factors. A broad range of antiretroviral host restriction factors has been identified in mammalian species. The best-described primate host restriction factors are APOBEC3F/G and TRIM5␣. APOBEC3F/G are cytidine deaminases which exert a late block to retroviral replication, inhibiting the virus in target cells rather than producer cells (29), whereas TRIM5␣ exerts a dominant block to infection immediately after viral entry into the cell through the inhibition of reverse transcription (30).TRIM5␣ is a member of the tripartite motif family of proteins, also called RBCC proteins, because of the presence of a RING domain (C3HC4 type), one or two B boxes, and a coiled-coil region in an ordered arrangement from N terminus to C terminus (23). Six isoforms of TRIM5 have been identified in mammals (26). These proteins have been shown to form homo-and heteromultimers, although only homomultimers of TRIM5␣ have been shown to restrict lentiviruses (3,8,15,...

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Enhanced replication of HIV‐1 in vivo in pigtailed macaques (Macaca nemestrina)

Cited by 15 publications

References 11 publications

Dynamics of Simian Immunodeficiency Virus SIVmac239 Infection in Pigtail Macaques

Dynamics of Simian Immunodeficiency Virus SIVmac239 Infection in Pigtail Macaques

Host Restriction Factors APOBEC3G/3F and Other Interferon-Related Gene Expressions Affect Early HIV-1 Infection in Northern Pig-Tailed Macaque (Macaca leonina)

Novel TRIM5 Isoforms Expressed byMacaca nemestrina

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