Virologic and Serologic Characteristics of a Natural Chimpanzee Lentivirus Infection

Peeters, Martine; Janssens, Wouter; Haesevelde, M Vanden; Fransen, Katrien; Willems, Betty; Heyndríckx, Leo; Kestens, Luc; Piot, Peter; Groen, G van der; Heeney, Jonathan L.

doi:10.1006/viro.1995.1407

Cited by 21 publications

(26 citation statements)

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“…In the Han2-infected animals marked follicular hyperplasia was seen only in one of the two infected animals in one lymph node biopsy, taken 21 weeks after infection. In contrast, lymph node biopsies taken from ch-No, naturally infected with an HIV-1-related virus (designated SIV cpz ), 48 had marked hyperplasia and substantial infiltration of CD8 1 T cells. Also, in ch-Ni, which was infected by blood transfusion from ch-No, marked follicular hyperplasia with infiltrating CD8 1 T cells was seen from 6 weeks after infection onward.…”

Section: Hiv-1-infected Chimpanzees Maintain Normal Lymph Node Morphomentioning

confidence: 84%

The Relative Resistance of HIV Type 1-Infected Chimpanzees to AIDS Correlates with the Maintenance of Follicular Architecture and the Absence of Infiltration by CD8+ Cytotoxic T Lymphocytes

Koopman

Haaksma²,

Velden³

et al. 1999

AIDS Research and Human Retroviruses

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Lymphoid tissues are the focus of critical events in HIV pathogenesis. Persistent and high levels of virus production, extensive trapping of virus particles in germinal centers, and progressive degenerative changes in lymph node architecture are characteristics of progressive HIV-1 infection. Infiltrates of granzyme B- and TIA-expressing CD8+ "cytotoxic" T lymphocytes (CTLs) precede involution of germinal centers in humans who develop AIDS. Similar to humans, HIV-1 infection in chimpanzees is active and persistent. However, in contrast to humans, they remain relatively resistant to AIDS. Lymph node biopsies from chimpanzees infected with HIV-1 or a related chimpanzee lentivirus were studied for the level and pattern of virus expression, changes in lymphoid architecture, CD8+ T cell infiltrates and the presence or absence of CTL markers. In stark contrast to HIV-1-infected humans, lymph nodes from infected chimpanzees had little virus deposition in germinal centers and a paucity of virus-expressing cells. Although some of the lymph nodes examined from infected animals had moderate follicular hyperplasia with infiltrating CD8+ T cells, none had evidence of follicular fragmentation. Most importantly, in marked contrast to infected humans, CD8+ T cells infiltrating the germinal center were negative for the CTL marker granzyme B. This evidence suggests that the infiltration of CD8+ CTLs into the germinal centers of lymph nodes may be a key determinant in AIDS pathogenesis.

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Section: Hiv-1-infected Chimpanzees Maintain Normal Lymph Node Morphomentioning

confidence: 84%

The Relative Resistance of HIV Type 1-Infected Chimpanzees to AIDS Correlates with the Maintenance of Follicular Architecture and the Absence of Infiltration by CD8+ Cytotoxic T Lymphocytes

Koopman

Haaksma²,

Velden³

et al. 1999

AIDS Research and Human Retroviruses

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“…ϩ -T-cell depletion or disease (51,52,56,66). Host, viral, or environmental factors could explain the different outcome of HIV-1 and SIVcpz infection of humans and chimpanzees, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Both are infected with the highly divergent SIVcpz-ant strain (55,80). ch-No was infected in Zaire, whereas ch-Ni was exposed to blood from cage mate ch-No (56,79).…”

Section: Methodsmentioning

confidence: 99%

Nef Proteins from Simian Immunodeficiency Virus-Infected Chimpanzees Interact with p21-Activated Kinase 2 and Modulate Cell Surface Expression of Various Human Receptors

Kirchhoff¹,

Schindler²,

Bailer³

et al. 2004

J Virol

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The accessory Nef protein allows human immunodeficiency virus type 1 (HIV-1) to persist at high levels and to cause AIDS in infected humans. The function of HIV-1 group M subtype B nef alleles has been extensively studied, and a variety of in vitro activities believed to be important for viral pathogenesis have been established. However, the function of nef alleles derived from naturally simian immunodeficiency virus (SIV)-infected chimpanzees, the original host of HIV-1, or from the HIV-1 N and O groups resulting from independent zoonotic transmissions remains to be investigated. In the present study we demonstrate that SIVcpz and HIV-1 group N or O nef alleles down-modulate CD4, CD28, and class I or II MHC molecules and up-regulate surface expression of the invariant chain (Ii) associated with immature major histocompatibility complex (MHC) class II. Furthermore, the ability of Nef to interact with the p21-activated kinase 2 was generally conserved. The functional activity of HIV-1 group N and O nef genes did not differ significantly from group M nef alleles. However, SIVcpz nef genes as a group showed a 1.8-and 2.0-fold-higher activity in modulating CD28 (P ‫؍‬ 0.0002) and Ii (P ‫؍‬ 0.016) surface expression, respectively, but were 1.7-fold less active in down-regulating MHC class II molecules (P ‫؍‬ 0.006) compared to HIV-1 M nef genes. Our finding that primary SIVcpz nef alleles derived from naturally infected chimpanzees modulate the surface expression of various human cellular receptors involved in T-cell activation and antigen presentation suggests that functional nef genes helped the chimpanzee virus to persist efficiently in infected humans immediately after zoonotic transmission.

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“…Many reasons argue against the widespread use of chimpanzees in research, including the ethical problems involved in the use of an endangered species, budgetary problems, and the very low induction of simian AIDS either from HIV-1 or its ancestor simian immunodeficiency virus cpz (SIVcpz) in infected chimpanzees (25,26,30,57,58,60,63).…”

mentioning

confidence: 99%

Multiple Restrictions of Human Immunodeficiency Virus Type 1 in Feline Cells

Münk

Zielonka

Constabel

et al. 2007

J Virol

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The productive replication of human immunodeficiency virus type 1 (HIV-1) occurs exclusively in defined cells of human or chimpanzee origin, explaining why heterologous animal models for HIV replication, pathogenesis, vaccination, and therapy are not available. This lack of an animal model for HIV-1 studies prompted us to examine the susceptibility of feline cells in order to evaluate the cat (Felis catus) as an animal model for studying HIV-1. Here, we report that feline cell lines harbor multiple restrictions with respect to HIV-1 replication. The feline CD4 receptor does not permit virus infection. Feline T-cell lines MYA-1 and FeT-1C showed postentry restrictions resulting in low HIV-1 luciferase reporter activity and low expression of viral Gag-Pol proteins when pseudotyped vectors were used. Feline fibroblastic CrFK and KE-R cells, expressing human CD4 and CCR5, were very permissive for viral entry and HIV-long terminal repeat-driven expression but failed to support spreading infection. KE-R cells displayed a profound block with respect to release of HIV-1 particles. In contrast, CrFK cells allowed very efficient particle production; however, the CrFK cellderived HIV-1 particles had low specific infectivity. We subsequently identified feline apolipoprotein B-editing catalytic polypeptide 3 (feAPOBEC3) proteins as active inhibitors of HIV-1 particle infectivity. CrFK cells express at least three different APOBEC3s: APOBEC3C, APOBEC3H, and APOBEC3CH. While the feAPOBEC3C did not significantly inhibit HIV-1, the feAPOBEC3H and feAPOBEC3CH induced G to A hypermutations of the viral cDNA and reduced the infectivity ϳ10-to ϳ40-fold.Like many retroviruses, human immunodeficiency virus type 1 (HIV-1) has a very limited host range; spreading replication is seen only in Homo sapiens and by artificial inoculation in the close relative the chimpanzee (Pan troglodytes) (2, 16), preventing the setup of an efficient small animal model for HIV-1 research. Many reasons argue against the widespread use of chimpanzees in research, including the ethical problems involved in the use of an endangered species, budgetary problems, and the very low induction of simian AIDS either from HIV-1 or its ancestor simian immunodeficiency virus cpz (SIVcpz) in infected chimpanzees (25,26,30,57,58,60,63).In general, the tropism of HIV-1 in human tissue is determined by the expression of its receptor protein CD4 together with CCR5 or CXCR4 chemokine receptors. Simian CD4 but not murine CD4 supports entry of HIV-1 (15, 33). HIV-1 entry through receptor-mediated membrane fusion is required for reverse transcription of the viral genomic RNA into a doublestranded DNA molecule. Murine T cells show early postentry restriction of HIV-1 at reverse transcription (3). In simian cells, a related restriction of HIV-1, but not of SIVs (5, 10, 53), involves the simian TRIM5␣ protein, which leads to increased viral uncoating and thereby suppresses reverse transcription (73). Since HIV-1 does not show spreading replication in nonhuman cells, cell type-and t...

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Virologic and Serologic Characteristics of a Natural Chimpanzee Lentivirus Infection

Cited by 21 publications

References 0 publications

The Relative Resistance of HIV Type 1-Infected Chimpanzees to AIDS Correlates with the Maintenance of Follicular Architecture and the Absence of Infiltration by CD8+ Cytotoxic T Lymphocytes

The Relative Resistance of HIV Type 1-Infected Chimpanzees to AIDS Correlates with the Maintenance of Follicular Architecture and the Absence of Infiltration by CD8+ Cytotoxic T Lymphocytes

Nef Proteins from Simian Immunodeficiency Virus-Infected Chimpanzees Interact with p21-Activated Kinase 2 and Modulate Cell Surface Expression of Various Human Receptors

Multiple Restrictions of Human Immunodeficiency Virus Type 1 in Feline Cells

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