T Cell Responses to Human Endogenous Retroviruses in HIV-1 Infection
The human genome contains a number of remnants or fossils of ancient viral infections referred to as human endogenous retroviruses (HERV). Like fossils, these HERV are usually considered to be dead or inert as under normal circumstances, HERVs are functionally defective or controlled by host factors. However, recent work has demonstrated that T cells in the human immune system respond to HERV when a person is infected with the human immunodeficiency virus (HIV). In HIV-1-infected individuals, intracellular defense mechanisms are compromised. The T cells responding to HERV share characteristics with T cells that effectively control cytomegalovirus, a common chronic viral infection. T cells responding to HERV can also kill target cells carrying HERV protein. For some HIV-positive people, the strength of their response against HERV is related to having a lower HIV viral load. This study has important implications for new directions in HIV vaccine research. One of the key obstacles to creating an effective HIV vaccine is overcoming the ability of some of the virus variants produced when HIV evades the immune responses that the body mounts to control infections.
The authors hypothesized that HIV-1 infection would remove or alter controls on HERV activity. Expression of HERV could potentially stimulate a T cell response to HERV antigens, and in regions of HIV-1/HERV similarity, these T cells could be cross-reactive. They show that the levels of HERV production in HIV-1-positive individuals exceed those of HIV-1-negative controls. To investigate the impact of HERV activity on specific immunity, they examined T cell responses to HERV peptides in 29 HIV-1-positive and 13 HIV-1-negative study participants. There was an inverse correlation between anti-HERV T cell responses and HIV-1 plasma viral load. In HIV-1-positive individuals, HERV-specific T cells are capable of killing cells presenting their cognate peptide. These data indicate that HIV-1 infection leads to HERV expression and stimulation of a HERV-specific CD8+ T cell response. HERV-specific CD8+ T cells have characteristics consistent with an important role in the response to HIV-1 infection: a phenotype similar to that of T cells responding to an effectively controlled virus (cytomegalovirus), an inverse correlation with HIV-1 plasma viral load, and the ability to lyse cells presenting their target peptide. These characteristics suggest that elicitation of anti-HERV-specific immune responses is a novel approach to immunotherapeutic vaccination. As endogenous retroviral sequences are fixed in the human genome, they provide a stable target, and HERV-specific T cells could recognize a cell infected by any HIV-1 viral variant. HERV-specific immunity is an important new avenue for investigation in HIV-1 pathogenesis and vaccine design. If T cells that recognize HERV can stably target HIV-infected cells, they could be an important factor in controlling HIV infection.
T Cell Responses to Human Endogenous Retroviruses in HIV-1 Infection. 2007 PLoS Pathog 3(11): e165
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Tags: Biology, Health, HIV/AIDS, Medicine, Microbiology, Science, Vaccines, Virology
For a fun, science fiction story using HERV see Greg Bear’s “Darwin’s Radio” and “Darwin’s Children”
Is it possible that the ‘telomeres’(genetic clocks), which contains a reverse transcriptase (hTERT) are endogenous retroviral remnants too?