R5 and syncitia forming virus
Feb 12, 2005
Is syncitium formation limited to lymphatic tissues? Are there any studies mapping reserviors and/or incidence of syncitium formation using needle biopsy. Are cells involved with syncitia terminal or are they immortalized? If terminal, how long do they survive? What is the evidence that R5 tropic virus does not form syncitia, and X4 virus does. I have read that Kaletra preferentially suppresses X4 virus in infants. Is this true and what might the mechanism be? With patients who have had lymphectomy, what was the resultant virological profile/tissue damage? I seem to have a localized symptomatic profile of pain in the lymph nodes of my neck, timed with taking my medication Kaletra. I am also taking Epivir and Viread but the symptom is associated with Kaletra. It is as if my neck is the primary locus of infection. There is no swelling and the pain is sharp not dull as with lymphadenopathy. My instinct is to have them excised or injected with siRNA against HIV or some other radical treatment. It is quite bothersome. I have asked my primary care doctor, but he keeps his cards pretty close as I think I intimidate him with a barrage of questions, some of which he can't answer and he doesn't want to speculate. Thank you for any contribution you can make. Speculation is encouraged.
Response from Dr. Pierone
Hello and thanks for posting. I can share the few tidbits that I know about syncytia formation and the relevance of this phenomenon to the natural history of HIV infection.
Syncytia formation refers to the observation that HIV infected monocytes and macrophages can fuse together in a rather large conglomeration of cells. This syncitium may occur in lymphoid tissues, bone marrow, and brain. The bad news about syncytia formation is that it enables an HIV-infected macrophage to bring dozens of previously uninfected macrophages into the fold (so to speak) and render them useless. This syncitium of immune cells does not participate in further general immune function and probably represents an attempt to neutralize the HIV-infected macrophage that started the process. The capacity for syncitia formation is not universal in HIV infection. Syncitia forming virus tends to emerge later in the course of infection and is associated with a more rapid decline in CD4 cells.
HIV can be divided into two general categories CCR5 tropic virus and CXCR4 tropic virus. This distinction is based on the predominant type of co-receptors. HIV attaches to cells via a CD4 receptor and requires one of these two co-receptors to get in. Studies have clearly demonstrated that the CXCR4 tropic virus is capable of syncytia formation, but CCR5 tropic virus is not. Patients with low CD4 counts are more likely to have both CXCR4 and CCR5 (dual tropic) virus. CCR5 inhibitors are now in large scale clinical trials and we are now routinely testing patients in these trials to see which type of virus they harbor. It is likely that this testing will become available for clinical care if these agents live up to their promise.
Standard combination antiretroviral therapy suppresses both variants and leads to control of viral replication in the majority of patients. Kaletra, Epivir, and Viread is a very potent combination and should be controlling viral replication unless resistance is present. I suspect your symptoms might be an unusual side effect of Kaletra, although knowing your viral load/CD4 status might help (since this is speculative). I doubt you need radical treatment (and siRNA is preclinical), it just may be that a change in regimen would help out. Have you been on this regimen long term and has it produced complete viral suppression with immune reconstitution?
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