In this study, we describe two cases of human immunodeficiency virus type 1 (HIV-1) intersubtype superinfection with CRF01_AE and subtype B strains, which occurred in two injection drug users participating in a prospective cohort study in Bangkok, Thailand. In both cases, the superinfecting strain was detected by molecular and serologic analyses several weeks after complete seroconversion to the primary infection with a strain belonging to a different subtype. Superinfection occurred despite specific T-cell and humoral antibody responses to the primary virus. In both cases, cross-subtype immune responses were limited or absent prior to the second infection. These data show that, in some individuals, the quality and quantity of the immune response elicited by primary HIV-1 infection may not protect against superinfection. This finding has important implications for vaccine design. HIV-1 vaccines, at a minimum, will need to include potent, broadly protective, conserved immunogens derived from several group M subtypes.
Although foamy viruses (FVs) are endemic among nonhuman primates, FV infection among humans is rare. Recently, simian foamy virus (SFV) infection was reported in 4 of 231 individuals occupationally exposed to primates (1.8%). Secondary transmission to spouses has not been seen, suggesting that while FV is readily zoonotic, humans may represent dead-end hosts. Among different simian species, SFV demonstrates significant sequence diversity within the U3 region of the long terminal repeat (LTR) and 3′ accessory open reading frames (ORFs). To examine if persistent human SFV infection and apparent lack of secondary transmission are associated with genetic adaptations in FV regulatory regions, we conducted sequence analysis of the LTR, internal promoter, ORF-1, and ORF-2 on a tissue culture isolate and peripheral blood mononuclear cell samples from a human infected with SFV of African green monkey origin (SFV-3). Compared to the prototype SFV-3 sequence, the LTR, internal promoter, and FV transactivator (ORF-1) showed sequence conservation, suggesting that FV zoonosis is not dependent on host-specific adaptation to these transcriptionally important regions. However, ORF-2 contains a number of deleterious mutations predicted to result in premature termination of protein synthesis. ORF-2 codes in part for the 60-kDa Bet fusion protein, proposed to be involved in the establishment of persistent cellular SFV infections. These results suggest that persistent human infection by SFV and reduced transmissibility may be influenced by the absence of a functional ORF-2.
Veterinarians encounter occupational exposures to animal material that place them at high risk for zoonoses. For feline retroviruses, the risk of zoonosis among healthy adult humans appears to be extremely small. However, potential for retroviral zoonosis, especially for viruses such as FeLV and FeFV that can replicate in human cells, cannot be eliminated, and universal precautions to reduce potential exposures should be used when handling sick cats.
Complete gp120 sequence information was obtained from eight persons with incident HIV-1 infections (four subtype E and four subtype B) who were part of a prospective injecting drug user (IDU) cohort in Bangkok, Thailand, during 1996-1998. The incident subtype E strains were similar to the prototype subtype E strain CM244 isolated in 1992 in northern Thailand. The incident subtype B strains displayed divergence, in both overall genetic distance and other significant gp120 characteristics, from the prototype North American subtype B strain HIV-MN. Recombinant gp120s derived from CM244 and HIV-MN strains are components of a vaccine that is undergoing phase III efficacy testing, begun in March 1999, among Bangkok area IDUs. The information presented here will be important in the evaluation of any breakthrough HIV-1 infections occurring among vaccinees during the vaccine trial and in ongoing vaccine development efforts in Thailand.
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