Rectal transmission of human immunodeficiency virus type 1 to chimpanzees. (49/30267)

Inoculation of chimpanzees with human immunodeficiency virus type 1 (HIV-1) has been used as a model system to define mechanisms of pathogenesis and to test protective efficacy of candidate HIV-1 vaccines. In most of these studies, the animals were inoculated intravenously. However, because HIV-1 is transmitted primarily across mucosal surfaces, future evaluations of vaccines should employ mucosal routes for administering infectious virus to immunized animals. To develop a model of rectal transmission of HIV-1, chimpanzees were exposed without trauma to 4 different HIV-1 strains at doses ranging from 200 to 10,000 TCIDs. Infection, characterized by seroconversion and repeated isolation of virus from lymphocytes, was established in 1 of 5 animals. This animal was sequentially inoculated with a subtype B and then an E strain and was infected with both strains. The results show that rectal exposure of adult chimpanzees to cell-free HIV-1 was not an efficient mode of transmission in this cohort.  (+info)

Endogenous mucosal antiviral factors of the oral cavity. (50/30267)

The oral cavity represents a unique site for mucosal transmission of human immunodeficiency virus type 1 (HIV-1). Unlike other mucosal sites, the oral cavity is rarely a site of HIV transmission despite detectable virus in saliva and oropharyngeal tissues of infected persons. One reason for this apparent paradox is the presence of endogenous mucosal antiviral factors. Innate inhibitory molecules, such as virus-specific antibodies, mucins, thrombospondin, and soluble proteins, have been identified and partially characterized from saliva. A recent addition to the growing list is secretory leukocyte protease inhibitor (SLPI), an approximately 12-kDa non-glycosylated protein found in serous secretions. Physiologic concentrations of SLPI potently protect adherent monocytes and activated peripheral blood mononuclear cells against HIV-1 infection. SLPI levels in saliva and semen but not breast milk approximate levels required for inhibition in vitro. Characterization of SLPI and other endogenous antiviral molecules may enhance our understanding of factors influencing mucosal HIV-1 transmission.  (+info)

Mucosal events in the pathogenesis of human immunodeficiency virus type 1 infection. (51/30267)

The interaction between human immunodeficiency virus type 1 (HIV-1) and primary mucosal cells isolated from normal human small intestine was investigated. Purified primary intestinal epithelial cells could transport cell-free HIV-1 to mononuclear cells, although the epithelial cells did not support viral replication. An unexpected finding was that primary intestinal macrophages were markedly less permissive to HIV-1 than were blood monocytes. The reduced permissiveness appeared to be due to the near absence of surface CCR5 on resident intestinal macrophages. Surface CCR5 could be up-regulated on the monocytes but not the intestinal macrophages by HIV-1 and gp120. Impaired permissiveness of intestinal macrophages to HIV-1 may play an important role in the low prevalence of HIV-1 mRNA-expressing macrophages in the lamina propria during HIV-1 infection in vivo. Characterization of the biologic properties of HIV-1 transport and infection in primary mucosal cells will be key to elucidating the pivotal role of mucosal surfaces in HIV-1 disease.  (+info)

Interactions of viruses and microparticles with apical plasma membranes of M cells: implications for human immunodeficiency virus transmission. (52/30267)

In the rectal mucosa, specialized M cells of the lymphoid follicle-associated epithelium conduct vesicular transport of antigens from the mucosal surface into organized mucosal lymphoid tissues, where immune responses are induced. Bacteria and viruses may exploit this mechanism to initiate mucosal or systemic infection. Viral pathogens, including reovirus, poliovirus, and possibly human immunodeficiency virus (HIV), can enter the intestinal or rectal mucosa by adhering to apical membranes of M cells, but the membrane components involved in these interactions are unknown. Glycoprotein coats on the apical surfaces of epithelial cells act as diffusion barriers that limit access of particles and microorganisms to membrane glycolipids and to certain oligosaccharide epitopes of enterocytes but allow selective adherence to M cells. The accessibility of membrane glycolipids of M cells, along with their active endocytic activity, could promote entry of HIV into the rectal mucosa.  (+info)

Human immunodeficiency virus type 1 (HIV-1) infection and expression in intestinal epithelial cells: role of protein kinase A and C pathways in HIV-1 transcription. (53/30267)

Human immunodeficiency virus (HIV) can infect human colon epithelial cell lines by both CD4-dependent and -independent mechanisms. The present studies assessed cellular factors that are important for HIV-1 transcription in human colon epithelial cells. The HIV-1 long terminal repeat (LTR) was shown to contain functional DNA cis-regulatory elements downstream of the viral transactivator-responsive element in the transcribed noncoding 5' leader sequence. These downstream regulatory elements, termed DSE, can bind c-Fos and JunD and transmit protein kinase C activation signals to the HIV LTR. Moreover, specific Jun and Fos transcription factors can transactivate HIV-1 provirus in human colon epithelial cells. The DSE also bind related proteins of the CREB/ATF family. In this regard, the DSE behave as 12-0-tetradecanoylphorbol 13-acetate responder element-like cAMP-responsive elements because they bind both AP-1 and CREB/ATF transcription factors, thereby permitting induction of the HIV-1 LTR by both protein kinase C and A activation signals.  (+info)

Infectious human immunodeficiency virus can rapidly penetrate a tight human epithelial barrier by transcytosis in a process impaired by mucosal immunoglobulins. (54/30267)

Mucosal surfaces are the main natural site of entry into the body for human immunodeficiency virus (HIV). Herein, an alternative mechanism for virus spread is described. The mechanism, which involves transcytosis of endosome-internalized HIV-particles, was generated by contact of HIV-infected cells with the apical surface of an epithelial cell line. Transcytosed viruses rapidly (in 20-30 min) access the serosal side of the epithelial barrier without infecting the epithelium itself. In turn, transcytosed HIV could infect host submucosal mononucleated target cells, and thus the infection could spread. An investigation was done to determine whether mucosal antibodies could block HIV transcytosis. Both secretory IgA (S-IgA) and IgG that were purified from colostrum from HIV-seropositive women impaired HIV transcytosis, irrespective of the level of the recombinant HIV envelope anti-gp160-specific activities in an ELISA. However, specific S-IgAs were more efficient than IgG. Therefore, mucosal-specific S-IgA to HIV-1 could be relevant to reducing infectivity of HIV-1 in corporeal fluids.  (+info)

Characterization of intestinal disease associated with human immunodeficiency virus infection and response to antiretroviral therapy. (55/30267)

Combination antiretroviral therapies suppress human immunodeficiency virus (HIV) in peripheral blood, but the effect in gastrointestinal mucosa is uncertain. The occurrence of pathogen-negative diarrhea led to speculation that local HIV infection is etiologic. Mucosal cellular reservoirs for HIV were documented by use of several techniques. Correlations were found among gastrointestinal symptoms, histopathologic findings, cytokine expression, lymphoid apoptosis, and HIV RNA and protein expression in rectal mucosa. Disproportionate depletion of mucosal CD4+ lymphocytes also was found. The short-term effects of antiretroviral therapies were examined to test the hypothesis that these changes are directly related to mucosal HIV infection. Therapy was associated with decreased symptoms, with comparable drops in peripheral blood and mucosal HIV RNA contents, and by increases in blood and mucosal CD4+ lymphocyte contents. In addition, the number of apoptotic cells also declined during therapy. These results suggest that HIV plays a direct role in producing intestinal dysfunction.  (+info)

Mucosal immune system of the human genital tract. (56/30267)

In contrast to the pronounced dominance of secretory IgA over other immunoglobulin isotypes in human saliva, tears, milk, and gastrointestinal fluids, secretions of both female and male genital tracts contain more IgG than secretory IgA. Both IgG and IgA are derived, to a variable degree, from the systemic immunoglobulin pool as well as from local synthesis. The origin of IgG- and IgA-plasma cell precursors destined for the genital tract is unknown, but indirect evidence suggests that mucosal inductive sites localized in the rectum, small intestine, and especially in the nasal cavity contribute such precursors to the female genital tract. Several studies indicated that intranasal immunization of various species, including humans, was efficient at inducing antigen-specific antibody responses in the female genital tract; however, whether this route is also effective in males has not been explored.  (+info)