scholarly journals Early Pathogenesis of Transmucosal Feline Immunodeficiency Virus Infection

2002 ◽  
Vol 76 (12) ◽  
pp. 6311-6322 ◽  
Author(s):  
Leslie A. Obert ◽  
Edward A. Hoover
Keyword(s):  
Lymph Nodes ◽  
Feline Immunodeficiency Virus ◽  
Mononuclear Cells ◽  
Target Cells ◽  
Lymphoid Tissues ◽  
Vaginal Mucosa ◽  
Feline Immunodeficiency Virus Infection ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Dna Pcr

ABSTRACT To identify the early target cells and tissues in transmucosal feline immunodeficiency virus (FIV) infection, cats were exposed to a clade C FIV isolate via the oral-nasal or vaginal mucosa and multiple tissues were examined by virus isolation coculture (VI), DNA PCR, catalyzed tyramide signal-amplified in situ hybridization (TSA-ISH), and immunohistochemistry between days 1 and 12 postinoculation (p.i.). FIV RNA was detected in tonsil and oral or vaginal mucosa as early as 1 day p.i. by TSA-ISH and in retropharyngeal, tracheobronchial, or external iliac lymph nodes and sometimes in spleen or blood mononuclear cells by day 2, indicating that regional and distant spread of virus-infected cells occurred rapidly after mucosal exposure. By day 8, viral RNA, DNA, and culturable virus were uniformly detected in regional and distant tissues, connoting systemic infection. TSA-ISH proved more sensitive than DNA PCR in detecting early FIV-infected cells. In mucosal tissues, the earliest demonstrable FIV-bearing cells were either within or subjacent to the mucosal epithelium or were in germinal centers of regional lymph nodes. The FIV+ cells were of either of two morphological types, large stellate or small round. Those FIV RNA+ cells which could be colabeled for a phenotype marker, were labeled for either dendritic-cell-associated protein p55 or T-lymphocyte receptor antigen CD3. These studies indicate that FIV crosses mucous membranes within hours after exposure and rapidly traffics via dendritic and T cells to systemic lymphoid tissues, a pathway similar to that thought to occur in the initial phase of infection by the human and simian immunodeficiency viruses.

scholarly journals Characterization of Morphologic Changes and Lymphocyte Subset Distribution in Lymph Nodes from Cats with Naturally Acquired Feline Immunodeficiency Virus Infection

1992 ◽  
Vol 29 (5) ◽  
pp. 391-399 ◽  
Author(s):  
B. A. Rideout ◽  
L. J. Lowernstine ◽  
C. A. Hutson ◽  
P. F. Moore ◽  
N. C. Pedersen
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Feline Immunodeficiency Virus ◽  
Clinical Stage ◽  
Relative Proportion ◽  
Prognostic Significance ◽  
Clinical Signs ◽  
Methyl Green ◽  
Feline Immunodeficiency Virus Infection ◽  
Immunodeficiency Virus

Lymph nodes were collected at biopsy or necropsy from 18 cats with naturally acquired symptomatic feline immunodeficiency virus (FIV) infection and from 18 seronegative cats. Thirty-five of the cats were domestic shorthairs and one was a Persian cross. The cats ranged from 7 months to 16 years of age and were mainly obtained from California veterinary practitioners, a California cattery, and a Veterinary Teaching Hospital. Based on clinical signs present at tissue collection, ten FIV-infected cats fell into the acquired immunodeficiency syndrome (AIDS)-related complex (ARC) clinical stage and eight in the terminal (AIDS) stage of FIV disease. All cats were FeLV negative by antigen ELISA. Histologic sections of lymph nodes from each cat were examined blindly and were categorized as hyperplastic, involuting, mixed hyperplastic and involuting, depleted, or normal based upon subjective evaluation of follicles and paracortex. The relative abundance of plasma cells was evaluated in methyl green pyronin (MGP) and hematoxylin and eosin-stained sections. Similar numbers of FIV-seropositive and -seronegative cats fell into each lymph node category. The only difference evident between FIV-infected cats and control cats was in the degree of plasmacytosis present; moderate to marked plasmacytosis was present in 13/18 FIV-infected cats but in only 3/18 control cats. Immunohistochemical staining of frozen lymph node sections from six FIV-infected cats and 12 control cats for CD4, CD8, Factor VIII-related antigen, and a B cell/follicular dendritic cell-specific (CD21-like) antigen revealed only a slight increase in the relative proportion of paracortical CD8+ lymphocytes versus CD4+ lymphocytes in lymph nodes from FIV-infected cats. These findings suggest that lymph node changes previously considered to be specific or highly suggestive of lentivirus-induced immunodeficiency disease are actually not specific but occur in FIV-seronegative cats as well. Despite this lack of specificity, lymph node changes seen in FIV-infected cats may have prognostic significance. All cats in the ARC stage had hyperplastic or mixed hyperplastic and involuting nodes, whereas those in the AIDS stage had either involuting or depleted nodes, which suggests that the clinical stage of disease correlates with the category of lymph node change.

Feline Immunodeficiency Virus Depletes Naïve (CD45RA+) CD4+ Lymphocytes from the Blood and Lymph Nodes of Domestic Cats during Acute Pediatric Infection.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3896-3896
Author(s):  
Calvin M. Johnson ◽  
Ayalew Mergia ◽  
Janelle Novak ◽  
Nazareth Gengozian
Keyword(s):  
T Lymphocytes ◽  
Lymph Nodes ◽  
Feline Immunodeficiency Virus ◽  
Pediatric Hiv ◽  
Lymphoid Tissues ◽  
Domestic Cats ◽  
Color Flow ◽  
Cd8 Cells ◽  
Immunodeficiency Virus ◽  
Cd4 Lymphocytes

Abstract Feline immunodeficiency virus (FIV) is an immunosuppressive lentivirus of domestic cats that serves as an animal model for the pathogenesis of CD4+ lymphopenia and thymus dysfunction in HIV infected humans. During most cases of adult and pediatric HIV infection, naïve CD4+ T lymphocytes recognized by the expression of the RA isoform of the leukocyte common antigen (CD45RA) are infected at a lower level than memory CD4+ T− lymphocytes; however, children with rapidly progressive disease due to thymic insufficiency harbor high levels of HIV within the CD45RA+ subpopulation. In FIV infected cats, the fate of naïve CD4 lymphocytes is unknown due to the lack of specific markers. Recently, a mAb (755) was reported to recognize the feline homologue to CD45RA, allowing the enumeration of naïve CD4 and CD8 lymphocytes in cats. The purpose of this study was to characterize the fate of CD4+CD45RA+ blood cells eight weeks after FIV infection. One-day-old kittens (n=6) were infected with virions either from a wild type clone (JSY3) or mutant ORF-A clone at equivalent reverse transcriptase units and compared to historical control data. Eight weeks after inoculation, the percentages of CD4+ and CD8+ cells belonging to the CD45RA+ subpopulation were measured by two-color flow cytometry. Both FIV inocula were associated with a reduction in total CD4+ lymphocytes from a median of 13% in controls to 8% in infected cats (P=0.004), contributing to a reduction in the CD4:CD8 ratio from 2.45 in controls to 0.76 in infected cats (P=0.007). The decline in CD4+ lymphocytes was attributable to a disproportionate loss of CD4+CD45RA+ cells: 69% of CD4+ cells were CD45RA+ in controls, as compared to 7% in FIV infected cats (P=0.004). In contrast, naïve CD8+ lymphocytes did not change significantly with FIV infection (67% of CD8+ cells were CD45RA+ in FIV infected cats as compared to 80% in controls). The distribution of CD45RA+ cells in the lymph nodes of FIV infected cats mirrored those in the blood. Together, these data suggest that acute FIV infection results in a rapid depletion of naïve CD4 lymphocytes throughout the blood and secondary lymphoid tissues, while proportions of naïve CD8 lymphocytes remain unchanged. CD4+CD45RA+ cells may be depleted during pediatric FIV infection through lytic infection or a transition to a memory phenotype lacking CD45RA.

scholarly journals nef Gene Is Required for Robust Productive Infection by Simian Immunodeficiency Virus of T-Cell-Rich Paracortex in Lymph Nodes

2003 ◽  
Vol 77 (7) ◽  
pp. 4169-4180 ◽  
Author(s):  
Chie Sugimoto ◽  
Kei Tadakuma ◽  
Isao Otani ◽  
Takashi Moritoyo ◽  
Hirofumi Akari ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Productive Infection ◽  
Lymphoid Tissues ◽  
Double Staining ◽  
Immunodeficiency Virus ◽  
Siv Infection ◽  
Infected Cells ◽  
Sivmac239 Infection

ABSTRACT The pathogenesis of AIDS virus infection in a nonhuman primate AIDS model was studied by comparing plasma viral loads, CD4+ T-cell subpopulations in peripheral blood mononuclear cells, and simian immunodeficiency virus (SIV) infection in lymph nodes for rhesus macaques infected with a pathogenic molecularly cloned SIVmac239 strain and those infected with its nef deletion mutant (Δnef). In agreement with many reports, whereas SIVmac239 infection induced AIDS and depletion of memory CD4+ T cells in 2 to 3 years postinfection (p.i.), Δnef infection did not induce any manifestation associated with AIDS up to 6.5 years p.i. To explore the difference in SIV infection in lymphoid tissues, we biopsied lymph nodes at 2, 8, 72, and 82 weeks p.i. and analyzed them by pathological techniques. Maximal numbers of SIV-infected cells (SIV Gag+, Env+, and RNA+) were detected at 2 weeks p.i. in both the SIVmac239-infected animals and the Δnef-infected animals. In the SIVmac239-infected animals, most of the infected cells were localized in the T-cell-rich paracortex, whereas in the Δnef-infected animals, most were localized in B-cell-rich follicles and in the border region between the paracortex and the follicles. Analyses by double staining of CD68+ macrophages and SIV Gag+ cells and by double staining of CD3+ T cells and SIV Env+ cells revealed that SIV-infected cells were identified as CD4+ T cells in either the SIVmac239 or the Δnef infection. Whereas the many functions of Nef protein were reported from in vitro studies, our finding of SIVmac239 replication in the T-cell-rich paracortex in the lymph nodes supports the reported roles of Nef protein in T-cell activation and enhancement of viral infectivity. Furthermore, the abundance of SIVmac239 infection and the paucity of Δnef infection in the T-cell-rich paracortex accounted for the differences in viral replication and pathogenicity between SIVmac239 and the Δnef mutant. Thus, our in vivo study indicated that the nef gene enhances SIV replication by robust productive infection in memory CD4+ T cells in the T-cell-rich region in lymphoid tissues.

scholarly journals Expression of CXCR4 on Feline Peripheral Blood Mononuclear Cells: Effect of Feline Immunodeficiency Virus Infection

2003 ◽  
Vol 77 (1) ◽  
pp. 709-712 ◽  
Author(s):  
Brian J. Willett ◽  
Celia A. Cannon ◽  
Margaret J. Hosie
Keyword(s):  
T Lymphocytes ◽  
Peripheral Blood Mononuclear Cells ◽  
Feline Immunodeficiency Virus ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Feline Immunodeficiency Virus Infection ◽  
Immunodeficiency Virus ◽  
Blood Mononuclear Cells

ABSTRACT CXCR4 expression on feline peripheral blood mononuclear cells (PBMC) was analyzed. While monocytes and B lymphocytes expressed CXCR4, no CXCR4 was detected on T lymphocytes, in stark contrast to the expression pattern on T lymphocytes from humans. In spite of the important role that CXCR4 plays in infection with feline immunodeficiency virus, expression on PBMC in vivo was unaffected by infection with either a primary or a cell culture-adapted virus strain.

Early Stages of Feline Immunodeficiency Virus Infection in Lymph Nodes and Spleen

1994 ◽  
Vol 10 (12) ◽  
pp. 1731-1738 ◽  
Author(s):  
JEAN-MARIE BACH ◽  
MARYSE HURTREL ◽  
LISA CHAKRABARTI ◽  
JEAN-PIERRE GANIERE ◽  
LUC MONTAGNIER ◽  
...  
Keyword(s):  
Virus Infection ◽  
Lymph Nodes ◽  
Feline Immunodeficiency Virus ◽  
Early Stages ◽  
Feline Immunodeficiency Virus Infection ◽  
Immunodeficiency Virus

scholarly journals Lymphatic Dissemination of Simian Immunodeficiency Virus after Penile Inoculation

2016 ◽  
Vol 90 (8) ◽  
pp. 4093-4104 ◽  
Author(s):  
Zhong-Min Ma ◽  
Joseph Dutra ◽  
Linda Fritts ◽  
Christopher J. Miller
Keyword(s):  
Immune Responses ◽  
Lymph Nodes ◽  
Simian Immunodeficiency Virus ◽  
Virus Replication ◽  
Target Cells ◽  
Lymphoid Tissues ◽  
Inguinal Lymph Nodes ◽  
Mucosal Surfaces ◽  
Immunodeficiency Virus ◽  
Rna Levels

ABSTRACTThe human immunodeficiency virus (HIV) is primarily transmitted by heterosexual contact, and approximately equal numbers of men and women worldwide are infected with the virus. Understanding the biology of HIV acquisition and dissemination in men exposed to the virus by insertive penile intercourse is likely to help with the rational design of vaccines that can limit or prevent HIV transmission. To characterize the target cells and dissemination pathways involved in establishing systemic simian immunodeficiency virus (SIV) infection, we necropsied male rhesus macaques at 1, 3, 7, and 14 days after penile SIV inoculation and quantified the levels of unspliced SIV RNA and spliced SIV RNA in tissue lysates and the number of SIV RNA-positive cells in tissue sections. We found that penile (glans, foreskin, coronal sulcus) T cells and, to a lesser extent, macrophages and dendritic cells are primary targets of infection and that SIV rapidly reaches the regional lymph nodes. At 7 days after inoculation, SIV had disseminated to the blood, systemic lymph nodes, and mucosal lymphoid tissues. Further, at 7 days postinoculation (p.i.), spliced SIV RNA levels were the highest in the genital lymph nodes, indicating that this is the site where the infection is initially amplified. By 14 days p.i., spliced SIV RNA levels were high in all tissues, but they were the highest in the gastrointestinal tract, indicating that the primary site of virus replication had shifted from the genital lymph nodes to the gut. The stepwise pattern of virus replication and dissemination described here suggests that vaccine-elicited immune responses in the genital lymph nodes could help prevent infection after penile SIV challenge.IMPORTANCETo be the most effective, vaccines should produce antiviral immune responses in the anatomic sites of virus replication. Thus, understanding the path taken by HIV from the mucosal surfaces, which are the site of virus exposure, to the deeper tissues where the virus replicates will provide insight into where AIDS vaccines should produce immunity to be the most effective. In this study, we determined that, by day 7 after penile inoculation, SIV has moved first to the inguinal lymph nodes and replicates to high levels. Although the virus is widely disseminated to other tissues by day 7, replication is largely limited to the inguinal lymph nodes. The step-by-step movement of SIV from penile mucosal surfaces to the draining lymph nodes may allow an HIV vaccine that produces immunity in these lymph nodes to block HIV from establishing an infection in an exposed person.

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 Cytokine Response in Multiple Lymphoid Tissues during the Primary Phase of Feline Immunodeficiency Virus Infection

1998 ◽  
Vol 72 (12) ◽  
pp. 9436-9440 ◽  
Author(s):  
Gregg A. Dean ◽  
Niels C. Pedersen
Keyword(s):  
Lymph Nodes ◽  
Feline Immunodeficiency Virus ◽  
Lymphoid Tissues ◽  
Mesenteric Lymph Nodes ◽  
Cytokine Mrna ◽  
Cervical Lymph Nodes ◽  
Mesenteric Lymph ◽  
Immunodeficiency Virus ◽  
Ifn Γ

ABSTRACT Type 1 and 2 cytokine mRNA responses were measured at various time periods and in various lymphoid compartments during the acute stage (first 4 months) of feline immunodeficiency virus (FIV) infection in laboratory cats. Cytokine responses were correlated with virus replication. Virus was detected in plasma and tissue from day 14 postinfection (p.i.) onward, peaked at 56 to 70 days, and declined greatly by 70 days. Virus replication was highest in the thymus, followed by spleen, mesenteric lymph nodes, and cervical lymph nodes. Baseline cytokine levels were highest in the mesenteric lymph nodes and lowest in the cervical lymph nodes. Cytokine upregulation after FIV infection was most dramatic in the cervical lymph nodes, with the greatest increase in interleukin-10 (IL-10) and gamma interferon (IFN-γ). Cytokine transcription in the mesenteric lymph node increased above baseline by day 14 p.i. for IFN-γ, IL-12p40, IL-4, and IL-10, while elevations in the spleen were mainly for IFN-γ, IL-12p40 and IL-10. An increase in IFN-γ, IL-10, and IL-12p40 occurred in the thymus at day 56 p.i., concomitant with the onset of thymitis. In general, type 2 cytokines (IL-4 and IL-10) were increased greater than 1 log over baseline, while the elevations in type 1 cytokines were less than 1 log. In the tissues tested, CD4+ cells were the primary source of IL-2, IL-4, and IL-10. Both CD4+ and CD8+ cells produced IFN-γ, while no cytokine mRNA was detected in B cells. These results demonstrate the presence of a heterogeneous cytokine response in lymphoid tissues during the primary stage of FIV infection. The nature and intensity of the response differed from one compartment to the other and, in the case of the thymus, also with inflammatory changes. Although limited in scope, the present study confirms the usefulness of the FIV infection model in studying early cytokine events that lead to the secondary subclinical carrier state typical of most lentivirus infections.

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