The Potential of Immune Modulation in Therapeutic HIV-1 Vaccination

We discuss here some of the key immunological elements that are at the crossroads and need to be combined to develop a potent therapeutic HIV-1 vaccine. Therapeutic vaccines have been commonly used to enhance and/or recall pre-existing HIV-1-specific cell-mediated immune responses aiming to suppress virus replication. The current success of immune checkpoint blockers in cancer therapy renders them very attractive to use in HIV-1 infected individuals with the objective to preserve the function of HIV-1-specific T cells from exhaustion and presumably target the persistent cellular reservoir. The major latest advances in our understanding of the mechanisms responsible for virus reactivation during therapy-suppressed individuals provide the scientific basis for future combinatorial therapeutic vaccine development.

Identification of viruses from fungal transcriptomes

ABSTRACTViruses infecting fungi are referred to as mycoviruses. Here, we carried out in silico mycovirome studies using public fungal transcriptomes. We identified 468 virus-associated contigs assigned to five orders, 21 families, 26 genera, and 88 species. We assembled 120 viral genomes with diverse RNA and DNA genomes. The phylogenetic tree and genome organization unveiled the possible host origin of mycovirus species and diversity of their genome structures. Most identified mycoviruses were originated from fungi; however, some mycoviruses had strong phylogenetic relationships with those from insects and plants. The viral abundance and mutation frequency of mycoviruses were very low; however, the compositions and populations of mycoviruses were very complex. Although coinfection of diverse mycoviruses in the fungi was common in our study, most mycoviromes had a dominant virus species. The compositions and populations of mycoviruses were more complex than we expected. Monilinia viromes revealed that there were strong deviations in the composition of viruses and viral abundance among samples. Gigaspora viromes showed that the chemical strigolactone might promote virus replication and mutations, while symbiosis with endobacteria might suppress virus replication and mutations. This study revealed the diversity and host distribution of mycoviruses.

PA28γ is a novel corepressor of HTLV-1 replication and controls viral latency

Key PointsPA28g acts as a co-repressor of HTLV-1 p30 to suppress virus replication and is required for the maintenance of viral latency. HTLV-1 has evolved a unique function mediated by its posttranscriptional repressor p30, which is not found in HTLV-2.

Initiation of Antiretroviral Therapy 48 Hours after Infection with Simian Immunodeficiency Virus Potently Suppresses Acute-Phase Viremia and Blocks the Massive Loss of Memory CD4+ T Cells but Fails To Prevent Disease

ABSTRACT We investigated whether a 28-day course of potent antiretroviral therapy, initiated at a time point (48 h postinoculation) following simian immunodeficiency virus (SIV) inoculation when the acquisition of a viral infection was virtually assured, would sufficiently sensitize the immune system and result in controlled virus replication when treatment was stopped. The administration of tenofovir 48 h after SIV inoculation to six Mamu-A*01-negative rhesus macaques did, in fact, potently suppress virus replication in all of the treated rhesus macaques, but plasma viral RNA rapidly became detectable in all six animals following its cessation. Unexpectedly, the viral set points in the treated monkeys became established at two distinct levels. Three controller macaques had chronic phase virus loads in the range of 1 × 103 RNA copies/ml, whereas three noncontroller animals had set points of 2 × 105 to 8 × 105 RNA copies/ml. All of the noncontroller monkeys died with symptoms of immunodeficiency by week 60 postinfection, whereas two of the three controller animals were alive at week 80. Interestingly, the three controller macaques each carried major histocompatibility complex class I alleles that previously were reported to confer protection against SIV, and two of these animals generated cytotoxic T-lymphocyte escape viral variants during the course of their infections.

Nonpulmonary manifestations of cytomegalovirus infection in immunocompromised patients.

Nonpulmonary manifestations of cytomegalovirus (CMV) infection in immunocompromised patients include chorioretinitis, gastrointestinal infection, and central nervous system disease. Diagnosis of end organ disease, especially in the gastrointestinal tract, is best substantiated by histologic evidence of CMV inclusions. Positive cultures of CMV provide evidence for supporting infection but do not define actual end organ disease. Satisfactory treatment of the disease can be accomplished with ganciclovir or foscarnet, although these agents only suppress virus replication. In many instances, severe CMV-induced end organ disease in immunocompromised patients will progress despite treatment. In some instances, resistance to the antiviral agent is the basis for drug failure. Patients at high risk for CMV disease can be identified, and studies of prophylaxis are in progress.