Characterisation of simian immunodeficiency virus-infected cells in pigtail macaques. 2012

Wendy R Winnall, and Amy Sexton, and Sheilajen Alcantara, and Sarah Roath, and Robert De Rose, and Stephen J Kent
Department of Microbiology and Immunology, University of Melbourne, Royal Parade, Parkville, 3010 VIC, Australia. wwinnall@unimelb.edu.au

Defining which cells become infected with simian immunodeficiency virus (SIV) in vivo should assist in unravelling the pathogenesis of human immunodeficiency virus (HIV)/SIV infection. HIV/SIV infection of CD4(+) T cells resulted in down-regulation of CD3 and CD4 surface molecules in vitro, however this phenomenon is poorly characterised in vivo. Intracellular SIV p27 was studied by flow cytometry in serial blood samples and lymph node samples during acute infection of 17 SIVmac-infected pigtail macaques. Two weeks after infection, a mean of 56±6.8% the p27(+) cells were lymphocytes negative for surface CD4 and CD3, and indeed the highest proportion of SIV infected cells were found in the small subset of CD3(Lo)CD4(-)CD8(-) lymphocytes, indicating that infection has lead to down-regulation of these markers in vivo. Furthermore, the relative amount of SIV p27 within lymphocytes (based of mean fluorescence intensity) was higher in CD3(Lo)CD4(-) and CD3(-) infected cells than in CD3(+) or CD4(+) p27(+) populations, consistent with greater viral production in CD4(+) T cells down-regulating CD3 and CD4 molecules. The CD3(-)CD4(-) infected cells expressed T cell markers CD2 and CD5 and were negative for monocyte, NK and B cell markers. The majority of infected cells were CD28(+)CD95(+) central memory T cells. Surprisingly, p27(+) blood lymphocytes were mostly negative for activation markers CD25 and CD69, but most of the infected lymph nodes cells were activated. Our results characterise productively-infected macaque lymphocytes in vivo. The high proportion of SIV-infected lymphocytes that are CD3(-)CD4(-) has important implications for the in vivo study of pathogenesis of SIV/HIV infections.

UI MeSH Term Description Entries
D008254 Macaca nemestrina A species of the genus MACACA which inhabits Malaya, Sumatra, and Borneo. It is one of the most arboreal species of Macaca. The tail is short and untwisted. M. leonina,Macaca nemestrina leonina,Macaca nemestrina pagensis,Macaca nemestrina siberu,Macaca siberu,Monkey, Pig-Tailed,Pagai Macaque,Pig-Tail Macaque,Pig-Tailed Macaque,Pig-Tailed Monkey,M. pagensis,Macaca pagensis,Monkey, Pigtail,Monkey, Pigtailed,Pigtail Macaque,Macaque, Pagai,Macaque, Pig-Tail,Macaque, Pig-Tailed,Macaque, Pigtail,Monkey, Pig Tailed,Pagai Macaques,Pig Tail Macaque,Pig Tailed Macaque,Pig Tailed Monkey,Pig-Tail Macaques,Pig-Tailed Macaques,Pig-Tailed Monkeys,Pigtail Macaques,Pigtail Monkey,Pigtail Monkeys,Pigtailed Monkey,Pigtailed Monkeys
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014764 Viral Proteins Proteins found in any species of virus. Gene Products, Viral,Viral Gene Products,Viral Gene Proteins,Viral Protein,Protein, Viral,Proteins, Viral
D015302 Simian Immunodeficiency Virus Species of the genus LENTIVIRUS, subgenus primate immunodeficiency viruses (IMMUNODEFICIENCY VIRUSES, PRIMATE), that induces acquired immunodeficiency syndrome in monkeys and apes (SAIDS). The genetic organization of SIV is virtually identical to HIV. SIV (Simian immunodeficiency virus),Immunodeficiency Viruses, Simian,Simian Immunodeficiency Viruses,Immunodeficiency Virus, Simian
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D015704 CD4 Antigens 55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. They are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. T4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120. Antigens, CD4,CD4 Molecule,CD4 Receptor,CD4 Receptors,Receptors, CD4,T4 Antigens, T-Cell,CD4 Antigen,Receptors, Surface CD4,Surface CD4 Receptor,Antigen, CD4,Antigens, T-Cell T4,CD4 Receptor, Surface,CD4 Receptors, Surface,Receptor, CD4,Surface CD4 Receptors,T-Cell T4 Antigens,T4 Antigens, T Cell

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