Desialylation of Peripheral Blood Mononuclear Cells Promotes Growth of HIV-1

Abstract

Activation of peripheral blood CD4+ helper T lymphocytes establishes a permissive state for growth of HIV-1. Activated T lymphocytes expressed increased sialidase (neuraminidase) activity and were hyposialylated. Treatment of freshly isolated peripheral blood mononuclear cells (PBMCs) with microbial neuraminidase (NANase) or phytohemagglutinin (PHA) prior to infection at low multiplicity with T cell line-adapted HIV-1IIIB resulted in production of large amounts of p24 antigen and reverse transcriptase. In contrast, neither viral component was detected in the medium of mock-treated cells infected at a similar multiplicity through 21 days in culture. The titer of a stock solution of HIV-1IIIB was 1.4 +/- 0.18 log10 greater in NANase-treated PBMCs than in mock-treated cells; the titer was similarly raised 1.5 to 1.76 +/- 0.18 log10 in PHA-treated cells. Growth of the primary isolate HIV-1(91/US/056) was also enhanced in NANase-treated PBMCs; the titer of a stock solution of HIV-1(91/US/056 was 1.0 +/- 0.16 log10 greater in NANase-treated PBMCs than in mock-treated cells 7 days after infection. No enhancement of viral growth in PBMCs was detected when NANase was heat-inactivated or specifically inhibited with 2,3-dehydro-2-desoxy-N-acetyl-neuraminic acid prior to use. Treatment of PBMCs with NANase did not alter the distribution of lymphocyte subsets nor change the density of CD4 antigen per cell after 7 days in culture. Whereas PHA treatment of PBMCs was mitogenic, pretreatment with NANase was not; the amount of [3H]thymidine incorporated into DNA and culture growth characteristics were similar for NANase- and mock-treated cells. Thus, desialylation of PBMCs promoted a permissive state for growth of HIV-1 without affecting the rate of DNA synthesis or relative number of target CD4+ cells.

Recruitment of Murine Neutrophils in Vivothrough Endogenous Sialidase Activity

“…3). Functional changes in both PMN and peripheral blood mononuclear cells have been demonstrated with up to 30% desialylation (9,38,39). On the basis of the present studies, we cannot determine whether inhibition of endogenous sialidase activity altered PMN trafficking through modulation of global desialylation with changes in net surface charge, and/or by interfering with the removal of sialyl residues from specific glycoconjugates essential to PMN adhesion and migration, such as a ␤ 2 -integrin or the IL-8 receptor.…”

Resistance of Native, Oligomeric Envelope on Simian Immunodeficiency Virus to Digestion by Glycosidases

“…Two previous studies have shown that incubation of patient PBMCs with neuraminidase increased the efficiency of viral isolation (44,47). However, in those studies it was unclear whether the effects were on PBMC or virus.…”

Syncytium Formation and HIV-1 Replication Are Both Accentuated by Purified Influenza and Virus-associated Neuraminidase

“…As the surface of both HIV-1 and its natural target cells contain highly sialylated glycoconjugates, previous works have scrutinized the potential implication of sialic acid and neuraminidase activity in the HIV-1 life cycle. For example, Hu et al (15) reported that desialylation of HIV-1 increases virus infectivity, whereas others have reported that desialylation of freshly isolated human peripheral blood mononuclear cells (PBMCs) creates a cellular environment more suitable for virus growth (16,26). More recently, we reported that Arthrobacter-derived NA augmented HIV-1-mediated syncytium formation and the initial steps in the virus life cycle (i.e.…”

“…Thus, it has been proposed that other interactions between the virus and the cell surface are necessary to overcome the various factors that might jeopardize the first step in the life cycle of an intracellular parasite such as HIV-1. Accumulating evidence suggest that the activity of bacterially derived neuraminidase (NA, also termed sialidase) can also modulate replication of this retrovirus, including the attachment process, by reducing the level of sialylation of glycoconjugates expressed on the surface of viruses and target cells (15)(16)(17).…”