Molecular and Cellular Interactions of HIV-1/HTLV Coinfection and Impact on AIDS Progression
Claudio Casoli 1, Elisabetta Pilotti 1, Umberto Bertazzoni 1
1 NULL
*Correspondence: Claudio Casoli, Email not available
Abstract
In the last 10 years HIV-1/human T-cell leukemia virus (HIV-1/HTLV) coinfection has emerged as aworldwide health problem. The numbers of HIV-1/HTLV-1 coinfections in South America and Africaare increasing, as well as HIV-1/HTLV-2 coinfections in the USA and Europe. Coinfections by eitherHTLV-1 or HTLV-2 and HIV-1 frequently occur in persons with a history of injection drug use. SinceHTLV-1 preferentially infects CD4+ T-cells and HTLV-2 has a tropism for CD8+ T-cells, the influence ofcoinfection on HIV-1 disease progression may be different.The effect of HIV-1/HTLV-1 coinfection on HIV-1 pathogenesis is controversial as soluble factors producedby HTLV-1 infected cells can either enhance or suppress HIV-1 infection. In HTLV-1/HIV-1 coinfectedpatients, upregulation of HIV-1 expression was attributed to strong activation of cytokines thatpromoted HIV infection. The introduction of HAART has dramatically reduced HIV-1 morbidity andmortality, but has given rise to an increased number of inflammatory syndromes. While HAART is successfulfor controlling HIV disease, it has little impact on HTLV-1/2 genome expression. The consequenceof coinfection, even with HAART, may well be the reported increase in neurologic disease.Several epidemiologic and in vitro studies of the influence of HTLV infection on HIV-1 related AIDSprogression suggest that HTLV-1 infection can promote HIV-1 replication and accelerate the clinicalprogression to AIDS. However, other studies have not confirmed these observations. The differences instudy outcomes could be related to the occurrence of different HIV-1 phenotypes in clinical disease.In contrast, evidence points to a confirmed protective role of HTLV-2 that is manifested as improvedsurvival and delayed progression to AIDS. The protective effect may be the result of maintaining normal-range levels of CD4 and CD8 counts, lowering HIV replication, and immune activation. As a corollary,the number of long-term nonprogressors for AIDS in the HIV-1/HTLV-2 coinfected group was foundto be significantly higher than in HIV-1 monoinfected cases. Investigations of the natural factors inducedby HTLV-2 that influence HIV-1 replication show that CCL3L1 (an isoform of CCL3) is preferentially inducedin HTLV-2 exposed seronegative HIV individuals and in long-term nonprogressor HTLV-2/HIV-1coinfected persons. The CCL3L1 inhibits HIV replication and thus acts as a potent effector against bothHIV infection and disease progression. As a complement to upregulation of CCL3L1, other chemokinesand cytokines induced by HTLV-2 may contribute to induction of the Th1 response against invadingpathogens, in contrast to the dominant Th2 response that appears to favor HIV infection.The number of individuals with either single HIV-1 or HTLV-2 infection, in a cohort of Italian intravenousdrug users monitored for 20 years, decreased significantly over time. However, the magnitudeof HTLV-2 decrease was significantly less than that of HIV-1, pointing to the need for increased attentionto, and control of, HTLV infection. In conclusion, the long-term effects of HIV and HTLV coinfections are poorly understood and themechanisms of dysregulation of cellular biosynthesis by HTLV that impact HIV disease progressionremain elusive.
