GB virus-C – a virus without a disease: We cannot give it chronic fatigue syndrome

BACKGROUND: Chronic fatigue syndrome (CFS) is an illness in search of an infectious etiology. GB virus-C (GBV-C) virus is a flavivirus with cell tropism and host defense induction qualities compatible with a role in producing the syndrome. The GBV-C genome is detectable in 4% of the population and 12% of the population is seropositive. The present study evaluated the association between infection with GBV and CFS. METHODS: We used a commercial EIA to detect antibodies against the GBV-C E2 protein and a quantitative real-time RT-PCR assay to detect active GBV-C infection. Sera were from a case control study of CFS in Atlanta, Georgia. The Fisher's exact two-tailed test was used for statistical analysis. RESULTS: Two of 12 CFS patients and one of 21 controls were seropositive for prior GBV-C infection and one control had viral RNA detected, indicating active infection. The results are not statistically different. CONCLUSION: We found no evidence that active or past infection with GBV is associated with CFS

Tuberculosis unleashed: the impact of human immunodeficiency virus infection on the host granulomatous response to Mycobacterium tuberculosis.

The granuloma plays a critical role in the host immune response to Mycobacterium tuberculosis, containing the organism and confining it in a latent state in most infected individuals. Indeed, approximately one-third of the world's population has latent M. tuberculosis infection. However, over the past decade, the human immunodeficiency virus type 1 (HIV-1) pandemic has profoundly affected the incidence and clinicopathological features of tuberculosis. This review examines the immunological mechanisms whereby HIV-1 impairs the establishment, maintenance and function of the tuberculous granuloma

Dynamic variation in the cellular origin of HIV type 1 during treatment of tuberculosis in dually infected subjects.

HIV-1 replication remains elevated in dually infected HIV-1/TB subjects at completion of antituberculosis therapy. A viral immunocapture assay was used to examine the cellular origin of HIV-1 within plasma from HIV-1/TB subjects at time of diagnosis of pulmonary TB, at end of TB treatment, and 6 months after completion of treatment. Asymptomatic HIV-1-infected subjects without TB (HIV-1/C) served as controls. Both activated immature macrophage (CD36(+)) and CD4 T cell (CD26(+)) compartments contributed to viral load. Changes in the activation status of either cellular compartment paralleled their contribution to viral load. Levels of HIV-1 originating from activated (HLA-DR(+)) cells and from CD36(+) and CD26(+) mononuclear cells resolved to levels observed in HIV-1/C by the end of treatment. HIV-1 isolated by anti-CD3 immunocapture from HIV-1/TB patients remained significantly higher than from HIV-1/C patients at the end of TB treatment and at 12 months follow-up. Therefore, viral production by lymphocytes extends well beyond the completion of TB treatment

Immune activation and induction of HIV-1 replication within CD14 macrophages during acute Plasmodium falciparum malaria coinfection.

OBJECTIVES: To determine the impact of Plasmodium falciparum malaria coinfection and its treatment on cellular reservoirs of viral replication in HIV-1-infected persons and to relate this to changes in systemic immune activation. METHODS: Plasma samples were obtained from HIV-1-infected individuals (n = 10) at diagnosis of acute malaria, 4 weeks after parasite clearance and from HIV-infected aparasitemic controls (n = 10). Immunomagnetic HIV-1 capture analysis was used to determine the cellular origin of cell-free virus particles present in all 30 plasma samples and indices of immune activation were measured using enzyme-linked immunosorbent assays. RESULTS: Compared with controls, the detectable proportion of HIV-1 particles derived from CD14 macrophages and CD26 lymphocytes was increased in persons with acute malaria coinfection and correlated with markedly increased plasma concentrations of both proinflammatory cytokines and soluble markers of macrophage and lymphocyte activation. Parasite clearance following treatment with antimalarial drugs resulted in decreased detection of HIV-1 particles derived from the CD14 macrophage cell subset and correlated with a marked diminution in systemic immune activation. CONCLUSIONS: Acute P. falciparum malaria coinfection impacts virus-host dynamics in HIV-1-infected persons at the cellular level, notably showing a reversible induction of HIV-1 replication in CD14 macrophages that is associated with changes in immune activation

Sequential and Simultaneous Immunization of Rabbits with HIV-1 Envelope Glycoprotein SOSIP.664 Trimers from Clades A, B and C

We have investigated the immunogenicity in rabbits of native-like, soluble, recombinant SOSIP.664 trimers based on the env genes of four isolates of human immunodeficiency virus type 1 (HIV-1); specifically BG505 (clade A), B41 (clade B), CZA97 (clade C) and DU422 (clade C). The various trimers were delivered either simultaneously (as a mixture of clade A + B trimers) or sequentially over a 73-week period. Autologous, Tier-2 neutralizing antibody (NAb) responses were generated to the clade A and clade B trimers in the bivalent mixture. When delivered as boosting immunogens to rabbits immunized with the clade A and/or clade B trimers, the clade C trimers also generated autologous Tier-2 NAb responses, the CZA97 trimers doing so more strongly and consistently than the DU422 trimers. The clade C trimers also cross-boosted the pre-existing NAb responses to clade A and B trimers. We observed heterologous Tier-2 NAb responses albeit inconsistently, and with limited overall breath. However, cross-neutralization of the clade A BG505.T332N virus was consistently observed in rabbits immunized only with clade B trimers and then boosted with clade C trimers. The autologous NAbs induced by the BG505, B41 and CZA97 trimers predominantly recognized specific holes in the glycan shields of the cognate virus. The shared location of some of these holes may account for the observed cross-boosting effects and the heterologous neutralization of the BG505.T332N virus. These findings will guide the design of further experiments to determine whether and how multiple Env trimers can together induce more broadly neutralizing antibody response