scholarly journals Wide Range of Viral Load in Healthy African Green Monkeys Naturally Infected with Simian Immunodeficiency Virus

2000 ◽  
Vol 74 (24) ◽  
pp. 11744-11753 ◽  
Author(s):  
Simoy Goldstein ◽  
Ilnour Ourmanov ◽  
Charles R. Brown ◽  
Brigitte E. Beer ◽  
William R. Elkins ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Lymphoid Tissues ◽  
Plasma Viremia ◽  
Dna And Rna ◽  
Chlorocebus Pygerythrus ◽  
Natural Host Species ◽  
Wide Range ◽  
Immunodeficiency Virus ◽  
Green Monkeys

ABSTRACT The distribution and levels of simian immunodeficiency virus (SIV) in tissues and plasma were assessed in naturally infected African green monkeys (AGM) of the vervet subspecies (Chlorocebus pygerythrus) by limiting-dilution coculture, quantitative PCR for viral DNA and RNA, and in situ hybridization for SIV expression in tissues. A wide range of SIV RNA levels in plasma was observed among these animals (<1,000 to 800,000 copies per ml), and the levels appeared to be stable over long periods of time. The relative numbers of SIV-expressing cells in tissues of two monkeys correlated with the extent of plasma viremia. SIV expression was observed in lymphoid tissues and was not associated with immunopathology. Virus-expressing cells were observed in the lamina propria and lymphoid tissue of the gastrointestinal tract, as well as within alveolar macrophages in the lung tissue of one AGM. The range of plasma viremia in naturally infected AGM was greater than that reported in naturally infected sooty mangabeys. However, the degree of viremia in some AGM was similar to that observed during progression to AIDS in human immunodeficiency virus-infected individuals. Therefore, containment of viremia is an unlikely explanation for the lack of pathogenicity of SIVagm in its natural host species, AGM.

scholarly journals Rapid and Irreversible CD4+ T-Cell Depletion Induced by the Highly Pathogenic Simian/Human Immunodeficiency Virus SHIVDH12R Is Systemic and Synchronous

2002 ◽  
Vol 76 (1) ◽  
pp. 379-391 ◽  
Author(s):  
Tatsuhiko Igarashi ◽  
Charles R. Brown ◽  
Russell A. Byrum ◽  
Yoshiaki Nishimura ◽  
Yasuyuki Endo ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Virus Infection ◽  
Lymph Nodes ◽  
T Lymphocyte ◽  
Lymphoid Tissues ◽  
Highly Pathogenic ◽  
Dna And Rna ◽  
Immunodeficiency Virus

ABSTRACT Highly pathogenic simian/human immunodeficiency virus chimeric viruses are known to induce a rapid, irreversible depletion of CD4+ T lymphocytes in the peripheral blood of acutely infected macaque monkeys. To more fully assess the systemic effects of this primary virus infection, specimens were collected serially between days 3 and 21 postinfection from variety of lymphoid tissues (lymph nodes, thymus, and spleen) and gastrointestinal tract and examined by DNA and RNA PCR, in situ hybridization, and immunohistochemical assays. In addition, the lymphoid tissues were evaluated by fluorescence-activated cell sorting. Virus infection was initially detected by DNA PCR on day 3 postinfection in lymph node samples and peaked on day 10 in the T-lymphocyte-rich areas of this tissue. CD4+ T-cell levels remained stable through day 10 in several lymphoid tissue specimens examined but fell precipitously between days 10 and 21. In situ terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assays revealed the accumulation of apoptotic cells during the second week of infection in both lymph nodes and thymus, which colocalized, to a large extent, to sites of both virus replication and CD4+ T-lymphocyte loss.

scholarly journals Characterization of Simian Immunodeficiency Virus Variants Anatomically Compartmentalized in Plasma and Milk in Chronically Infected African Green Monkeys

2016 ◽  
Vol 90 (19) ◽  
pp. 8795-8808
Author(s):  
Jonathon E. Himes ◽  
Carrie Ho ◽  
Quang N. Nguyen ◽  
Joshua D. Amos ◽  
Haolin Xu ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Host Species ◽  
Interleukin 12 ◽  
Transmission Rates ◽  
Postnatal Transmission ◽  
Natural Host Species ◽  
Immunodeficiency Virus ◽  
Cytokine Milieu ◽  
Hiv 1 ◽  
Green Monkeys

ABSTRACTUnlike human immunodeficiency virus type 1 (HIV-1)-infected humans, African-origin, natural simian immunodeficiency virus (SIV) hosts, such as African green monkeys (AGMs), sustain nonpathogenic SIV infections and rarely vertically transmit SIV to their infants. Interestingly, chronically SIV-infected AGMs have anatomically compartmentalized SIV variants in plasma and milk, whereas humans and SIV-infected rhesus monkeys (RMs), Asian-origin nonnatural SIV hosts, do not exhibit this compartmentalization. Thus, it is possible that AGM SIV populations in milk have unique phenotypic features that contribute to the low postnatal transmission rates observed in this natural host species. In this study, we explored this possibility by characterizing the infectivity, tropism, and neutralization susceptibility of plasma and milk SIVsabenvvariants isolated from chronically SIVsab92018ivTF-infected AGMs. AGM plasma and milk SIVsabenvpseudovirus variants exhibited similar infectivities, neutralization susceptibilities to autologous and heterologous plasma, and chemokine coreceptor usages for cell entry, suggesting similar abilities to initiate infection in a new host. We also assessed the cytokine milieu in SIV-infected AGM milk and compared it to that of SIV-infected RMs. MIP-1β, granulocyte colony-stimulating factor (G-CSF), interleukin-12/23 (IL-12/23), and IL-13 trended significantly higher in SIV-infected AGM milk than in that of RMs, while IL-18 and IL-6 trended significantly higher in SIV-infected RM milk than in that of AGMs. Taken together, our findings imply that nonviral maternal factors, such as the cytokine milieu, rather than unique characteristics of SIV populations in the milk contribute to the low postnatal transmission rates observed in AGMs.IMPORTANCEDue to the ongoing global incidence of pediatric HIV-1 infections, including many that occur via breastfeeding, development of effective vaccine strategies capable of preventing vertical HIV transmission through breastfeeding remains an important goal. Unlike HIV-1-infected humans, African green monkeys (AGMs), the natural SIV host species, sustain nonpathogenic SIV infections, rarely transmit the virus postnatally to their infants, and exhibit anatomically compartmentalized SIV populations in milk and plasma. Identifying unique features of the anatomically compartmentalized milk SIV populations could enhance our understanding of how AGMs may have evolved to avoid transmission through breastfeeding. While this study identified limited phenotypic distinctions between AGM plasma and milk SIV populations, potential differences in milk cytokine profiles of natural and nonnatural SIV hosts were observed. These findings imply the potential importance of nonviral factors in natural SIV host species, such as innate SIV/HIV immune factors in milk, as a means of naturally preventing vertical transmission.

scholarly journals Detecting the Simian Immunodeficiency Virus Reservoir as Viral DNA and RNA in Situ Simultaneously as a Model to Monitor Viral Latency

2014 ◽  
Vol 30 (3) ◽  
pp. 205-206
Author(s):  
Xavier Alvarez ◽  
Cecily Midkiff ◽  
Marcelo J. Kuroda ◽  
Mahesh Mohan ◽  
Andrew A. Lackner
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Viral Latency ◽  
Viral Dna ◽  
Dna And Rna ◽  
Immunodeficiency Virus

scholarly journals In situ hybridization and immunolabelling study of the early replication of simian immunodeficiency virus (SIVmacJ5) in vivo

2001 ◽  
Vol 82 (9) ◽  
pp. 2225-2234 ◽  
Author(s):  
Carmen Cantó-Nogués ◽  
Sue Jones ◽  
Rebecca Sangster ◽  
Peter Silvera ◽  
Robin Hull ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Simian Immunodeficiency Virus ◽  
Lymphoid Tissues ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Immunodeficiency Virus ◽  
Early Replication ◽  
Dna Pcr

The distribution of virus-infected cells in cynomolgus macaques was determined at 4, 7, 14 and 28 days following intravenous challenge with 1000 TCID50 of the wild-type simian immunodeficiency virus SIVmacJ5 (stock J5C). At each time-point, pairs of macaques were killed humanely and the presence of SIV was determined and quantified in blood, spleen, peripheral and mesenteric lymph nodes, thymus, lung and ileum by virus co-cultivation with C8166 cells, by quantitative DNA PCR or by in situ hybridization (ISH). At day 4 post-infection (p.i.), detection of the virus was sporadic. By day 7 p.i., however, significant SIV loads were detected in the blood and lymphoid tissues by DNA PCR and virus co-cultivation. Large numbers of cells expressing SIV RNA were detected in mesenteric lymph nodes by ISH and significantly fewer (P<0·05) in the spleen. Significant numbers of ISH-positive cells were also observed in sections of ileum. By day 14 p.i., the distribution of SIV was more even in all lymphoid tissues analysed. By day 28, most of the tissues were negative by ISH, but all remained positive by virus isolation and DNA PCR. Immunolabelling of sections of mesenteric lymph node with monoclonal antibodies specific for SIV envelope and Nef largely confirmed the observations from ISH. These results indicate that, even following intravenous challenge, a major site of the initial replication of SIV is gut-associated lymphoid tissue. Vaccines that induce protection at this site may therefore be superior, even against parenteral challenge.

scholarly journals DC-SIGN from African Green Monkeys Is Expressed in Lymph Nodes and Mediates Infection in trans of Simian Immunodeficiency Virus SIVagm

2004 ◽  
Vol 78 (2) ◽  
pp. 798-810 ◽  
Author(s):  
Mickaël J.-Y. Ploquin ◽  
Ousmane M. Diop ◽  
Nathalie Sol-Foulon ◽  
Lorenzo Mortara ◽  
Abdourahmane Faye ◽  
...  
Keyword(s):  
T Cells ◽  
Amino Acid ◽  
Lymph Nodes ◽  
Simian Immunodeficiency Virus ◽  
Transmission Factor ◽  
Predicted Amino Acid Sequence ◽  
Isolation And Characterization ◽  
Natural Host Species ◽  
Immunodeficiency Virus ◽  
Green Monkeys

ABSTRACT African green monkeys (AGMs) infected by simian immunodeficiency virus (SIV) SIVagm are resistant to AIDS. SIVagm-infected AGMs exhibit levels of viremia similar to those described during pathogenic human immunodeficiency virus type 1 (HIV-1) and SIVmac infections in humans and macaques, respectively, but contain lower viral loads in their lymph nodes. We addressed the potential role of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN; CD209) in viral dissemination. In previous studies, it has been shown that human DC-SIGN and macaque DC-SIGN allow transmission of HIV and SIVmac to T cells. Here, we looked at the ability of DC-SIGN derived from AGM lymph nodes to interact with SIVagm. We show that DC-SIGN-expressing cells are present mainly in the medulla and often within the cortex and/or paracortex of AGM lymph nodes. We describe the isolation and characterization of at least three isoforms of dc-sign mRNA in lymph nodes of AGMs. The predicted amino acid sequence from the predominant mRNA isoform, DC-SIGNagm1, is 92 and 99% identical to the corresponding human and rhesus macaque DC-SIGN amino acid sequences, respectively. DC-SIGNagm1 is characterized by the lack of the fourth motif in the repeat domain. This deletion was also detected in the dc-sign gene derived from thirteen animals belonging to five other African monkey species and from four macaques (Macaca fascicularis and M. mulatta). Despite three- to seven-amino-acid modifications compared to DC-SIGNmac, DC-SIGNagm1 allows transmission of SIVagm to T cells. Furthermore, AGM monocyte-derived dendritic cells (MDDC) expressed at least 100,000 DC-SIGN molecules and were able to transmit SIVagm to T cells. At a low multiplicity of infection (10−5 50% tissue culture infective doses/cell), viral transmission by AGM MDDC was mainly DC-SIGN dependent. The present study reveals that DC-SIGN from a natural host species of SIV has the ability to act as an efficient attachment and transmission factor for SIVagm and suggests the absence of a direct link between this ability and viral load levels in lymph nodes.

scholarly journals Induction of Mucosal Protection against Primary, Heterologous Simian Immunodeficiency Virus by a DNA Vaccine

2002 ◽  
Vol 76 (7) ◽  
pp. 3309-3317 ◽  
Author(s):  
Deborah Heydenburg Fuller ◽  
Premeela A. Rajakumar ◽  
Lawrence A. Wilson ◽  
Anita M. Trichel ◽  
James T. Fuller ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Dna Vaccine ◽  
Dna Sequences ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Effective Vaccine ◽  
Lymphoid Tissues ◽  
Mucosal Protection ◽  
Mucosal Transmission ◽  
Immunodeficiency Virus

ABSTRACT An effective vaccine against human immunodeficiency virus (HIV) should protect against mucosal transmission of genetically divergent isolates. As a safe alternative to live attenuated vaccines, the immunogenicity and protective efficacy of a DNA vaccine containing simian immunodeficiency virus (SIV) strain 17E-Fr (SIV/17E-Fr) gag-pol-env was analyzed in rhesus macaques. Significant levels of cytotoxic T lymphocytes (CTL), but low to undetectable serum antibody responses, were observed following multiple immunizations. SIV-specific mucosal antibodies and CTL were also detected in rectal washes and gut-associated lymphoid tissues, respectively. Vaccinated and naive control monkeys were challenged intrarectally with SIV strain DeltaB670 (SIV/DeltaB670), a primary isolate whose env is 15% dissimilar to that of the vaccine strain. Four of seven vaccinees were protected from infection as determined by the inability to identify viral RNA or DNA sequences in the peripheral blood and the absence of anamnestic antibody responses postchallenge. This is the first report of mucosal protection against a primary pathogenic, heterologous isolate of SIV by using a commercially viable vaccine approach. These results support further development of a DNA vaccine for protection against HIV.

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