Vaniambadi S. Kalyanaraman

Transfusion-associated acquired immunodeficiency syndrome. Evidence for persistent infection in blood donors.

To investigate whether infection with human T-cell lymphotropic virus/lymphadenopathy-associated virus (HTLV-III/LAV) may be persistent in asymptomatic persons and to correlate infection with seropositivity the authors performed virologic and serologic studies in 25 of 30 persons who were identified as being at high risk for the acquired immunodeficiency syndrome (AIDS) and who had donated blood to patients who later contracted transfusion-associated AIDS. High-risk donors were those who belonged to a high-risk population had AIDS or a closely related condition or had a low ratio of helper to suppressor T lymphocytes. The authors performed similar studies in 6 of the 24 patients with AIDS who had received donations from this group. HTLV-III/LAV was isolated from 22 of the 25 donors between 12 and 52 months (mean 28) after they had donated blood and from all 6 recipients between 14 and 37 months (mean 26) after they had received blood. Of the 22 virus-positive donors 2 have contracted AIDS 5 have generalized lymphadenopathy and 15 (68%) remain asymptomatic. Antibodies to HTLV-III/LAV were detectable by the enzyme-linked immunosorbent assay in serum samples obtained from each person at the time the virus was isolated. It is concluded that infection with HTLV-III/LAV may be persistent and asymptomatic for years. This demonstrates that viremic patients may be asymptomatic supports the use of serologic screening of donated blood to supplement current procedures for the prevention of transfusion-associated AIDS. (authors)

Biological characterization of noninfectious HIV-1 particles lacking the envelope protein

To understand the role of the HIV-1 envelope protein in the assembly of virus, we constructed a proviral clone of HIV-1 where the methionine initiator codon of the env gene was substituted with a translational stop codon. Upon DNA transfection into permissive cells in culture, this clone produces virus-like particles similar in size to parental virus but are noninfectious in human T-cells, promonocytic cells, and primary macrophages. This mutant readily recombines with a deletion mutant provirus lacking the entire gag-pol region producing a recombinant virus that is infectious. Substitution of the same initiator methionine codon with valine results in a leaky missense mutant provirus capable of a low level of Env protein synthesis that leads to a productive infection. Thus, the prototype initiation codon AUG is dispensable for virus infectivity. Further, the expression of the envelope protein is not a prerequisite for the assembly of the virus particles in the HIV-1 system. These noninfectious envelope-less particles revert readily to wild-type phenotype upon cotransfection with Env-producing plasmid DNAs.

Human T-cell leukemia virus type II: Primary structure analysis of the major internal protein, p24 and the nucleic acid binding protein, p15

The 24,000-molecular-weight major internal protein (p24) and the 15,000-molecular-weight nucleic acid binding protein (p15) of human T-cell leukemia virus type II (HTLV-II) were subjected to amino acid composition and amino-terminal amino acid sequence analysis. A comparison of amino acid composition of p24 and p15 of HTLV-II with those of the analogous proteins of HTLV-I revealed that these two proteins share overall similarity. Further, alignment of the amino-terminal amino acid sequence for the first 27 residues of p24 and 34 residues of p15 from HTLV-II showed extensive sequence homology with analogous proteins of HTLV-I. These data suggest that although disease associated with HTLV-I is malignant T-cell leukemia and that associated with HTLV-II is a relatively benign variant of hairy-cell leukemia, HTLV-I and HTLV-II are closely related to each other, at least in their gag-gene-encoded sequences.

Transfusion-Associated Acquired Immunodeficiency Syndrome: Evidence for Persistent Infection in Blood Donors

To investigate whether infection with human T-cell lymphotropic virus/lymphadenopathy-associated virus (HTLV-III/LAV) may be persistent in asymptomatic persons and to correlate infection with seropositivity, we performed virologic and serologic studies in 25 of 30 persons who were identified as being at high risk for the acquired immunodeficiency syndrome (AIDS) and who had donated blood to patients who later contracted transfusion-associated AIDS. High-risk donors were those who belonged to a high-risk population, had AIDS or a closely related condition, or had a low ratio of helper to suppressor T lymphocytes. We performed similar studies in 6 of the 24 patients with AIDS who had received donations from this group. HTLV-III/LAV was isolated from 22 of the 25 donors, between 12 and 52 months (mean, 28) after they had donated blood, and from all 6 recipients, between 14 and 37 months (mean, 26) after they had received blood. Of the 22 virus-positive donors, 2 have contracted AIDS, 5 have generalized lymphadenopathy, and 15 (68 per cent) remain asymptomatic. Antibodies to HTLV-III/LAV were detectable by the enzyme-linked immunosorbent assay in serum samples obtained from each person at the time the virus was isolated. We conclude that infection with HTLV-III/LAV may be persistent and asymptomatic for years. This demonstration that viremic patients may be asymptomatic supports the use of serologic screening of donated blood to supplement current procedures for the prevention of transfusion-associated AIDS.

ANTIBODIES TO HUMAN T-CELL LEUKEMIA VIRUS (HTLV) IN CHILDREN WITH ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS)

Six children previously documented with AIDS and seven age matched controls from a similar socio-economic environment were studied for the presence of antibodies (Ab) to HTLV. Additionally, 5 adult AIDS cases and 13 similarly matched adult controls were also examined for HTLV Ab. All determinations were done blindly by two assay systems: indirect membrane immunofluorescence (IF) using HTLV infected HUT-102 cells and Ab to structural proteins of HTLV by a radioimmune precipitation assay (RIP). All 6 pediatric AIDS cases were positive for IF-Ab while negative for RIP-Ab. In contrast, 6 of 7 pediatric controls were negative for IF-Ab and all 7 negative for RIP-Ab. The IF-Ab positive control child was only weakly positive. All pediatric AIDS cases had non-specific Ab directed against infected HUT-102 cells which required absorption. None of the pediatric controls had this non-specific Ab. All 5 adult AIDS patients were positive for IF-Ab while 2 were also positive for RIP-Ab. Two of 13 adult controls were weakly positive for IF-Ab and all negative for RIP-Ab. This data supports the concept that an HTLV-like virus is important in the etiology of AIDS.