Provirus mutations of
human T-lymphotropic virus 1 (
HTLV-1), mostly the lack of the 5=
long terminal repeat (LTR) genomic region, have been described and associated with severe
adult T cell leukemia/
lymphoma (
ATLL), non-sense
point mutations with low proviral load, and
Western blotting indeterminate results. Until now, no information concerning
provirus mutations of
HTLV-2 and its consequences, as well as those of
HTLV-1/2 in
HIV-coinfected individuals, had been described. Therefore, we searched for these
mutations in
provirus samples of 44
HIV/
HTLV-1- and 25
HIV/
HTLV-2-coinfected individuals. Using
protocols well established for amplification and sequencing of segments of the LTR, env, and
tax regions, we searched for defective type 1 particles that retain LTRs and lack internal sequences and type 2 particles that lack the 5=LTR region. In addition, using as references the prototypes ATK (
HTLV-1) and Mo (
HTLV-2), we searched for
point mutations in the LTR and synonyms and nonsynonymous
mutations and non-sense
mutations in env and
tax regions. Defective
HTLV-1 and
HTLV-2 provirus type 1 or 2 was detected in 31.8% of
HIV/
HTLV-1- and 32.0% of
HIV/
HTLV-2-coinfected individuals. Synonymous and nonsynonymous
mutations were identified mostly in
HTLV-2 and associated with lower levels of specific
antibodies. No non-sense
mutations that resulted in premature termination of Env and
Tax proteins were detected. On the contrary,
mutation in the
stop codon of Tax2a produced a long
protein characteristic of the HTLV-2c subtype. The
clinical significance of these
mutations in coinfected individuals remains to be defined, but they confirmed the lower
sensitivity of serological and
molecular diagnostic tests in
HIV/
HTLV-1/2
coinfections. IMPORTANCE
HTLV-1 and
HTLV-2 are endemic to
Brazil, and they have different effects in
HIV/
AIDS disease progression.
HIV/
HTLV-1 has been described as accelerating the progression to
AIDS and
death, while
HIV/
HTLV-2 slows the progression to
AIDS.
Provirus mutations of
HTLV-1 were implicated in severe
leukemia development and in problems in the
diagnosis of
HTLV-1; in contrast,
provirus mutations of
HTLV-2 had not been confirmed and associated with problems in
HTLV-2 diagnosis or
disease outcome. Nevertheless, data obtained here allowed us to recognize and understand the false-
negative results in serologic and molecular tests applied for
HTLV-1 and
HTLV-2 diagnosis. Defective
proviruses, as well as synonymous and nonsynonymous
mutations, were associated with the
diagnosis deficiencies. Additionally, since
HIV-1 and
HTLV-1 infect the same
cells (CD4 positive), the
production of
HIV-1 pseudotypes with
HTLV-1 envelope
glycoprotein during
HIV/
HTLV-1 coinfection cannot be excluded. Defective
provirus of
HTLV-2 and Tax2c is speculated to influence progression to
AIDS. (AU)