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Published on: September 1, 2015
Detection of a human intracisternal retroviral particle associated with CD4+ T-cell deficiency
S Gupta1, C E Ribak, S Gollapudi
1Department of Medicine, University of California, Irvine 92717.
Insights
A novel retrovirus, human intracisternal retroviral particles (HICRV), was found in patients with unexplained CD4+ T-cell deficiency. This discovery suggests HICRV may cause immune dysfunction in individuals without typical HIV risk factors.
Area of Science:
- Immunology
- Virology
- Retroviruses
Background:
- CD4+ T-cell deficiency and dysfunction are linked to various non-HIV-1 disorders.
- The causes of CD4+ T-cell immunodeficiency in these conditions are not fully understood.
Purpose of the Study:
- To investigate the potential role of novel retroviral agents in unexplained CD4+ T-cell immunodeficiency.
Main Methods:
- Detection of human intracisternal retroviral (HICRV) particles in cell lines exposed to patient mononuclear cells.
- Ultrastructural analysis and comparison with known retroviruses (HIV-1, HIV-2, HTLV-I, HTLV-II).
- Assay of reverse transcriptase activity, PCR for proviral DNA, and Western blot for antibody detection.
Main Results:
- HICRV particles, distinct from HIV and HTLV, were identified in a patient with severe CD4+ T-cell deficiency and their daughter with T-cell dysfunction.
- Patient's cells tested negative for HIV and HTLV, but serum showed antibodies against HICRV.
- Significant Mn2+-dependent reverse transcriptase activity was observed.
Conclusions:
- Human intracisternal retroviral particles (HICRV) may be associated with CD4+ T-cell immunodeficiency and dysfunction.
- This finding is significant for patients lacking risk factors for common retroviral infections like HIV and HTLV.
Abstract:
A number of non-human-immunodeficiency-virus (HIV) type 1 disorders are associated with CD4+ T-cell deficiency and dysfunction. However, the etiopathogenesis of CD4+ T-cell immunodeficiency in these disease states remains unclear. Human intracisternal retroviral (HICRV) particles were detected in a lymphoblastoid cell line exposed to mononuclear cells from a patient with severe CD4+ T-cell deficiency without risk factors for HIV infection. Ultrastructurally, the HICRV is distinct from HIV-1, HIV-2, human T-lymphotropic virus (HTLV) type I, and HTLV-II. Supernatants of activated mononuclear cells showed significant reverse transcriptase activity that was predominantly Mn2+ dependent. The patient's mononuclear cells were negative for HIV-1, HIV-2, HTLV-I, and HTLV-II proviruses as demonstrated by the lack of amplification by PCR. Also, the patient's serum was negative for antibodies to HIV-1, HTLV-I, and HTLV-II and for HIV-1 p24 antigen; however, serum was positive for antibodies against the HICRV as demonstrated by Western blot. Similar HICRV particles were detected in a lymphoblastoid cell line exposed to mononuclear cells from the patient's daughter, who showed CD4+ T-cell dysfunction. The HICRV may be associated with CD4+ T-cell immunodeficiency and dysfunction in patients without risk for HIV-1, HIV-2, HTLV-I, and HTLV-II.
