Kimberly Herard

Detailed characterization of transmitted HIV-1 variants in Uganda is fundamentally important to inform vaccine design, yet studies on the transmitted full-length strains of subtype D viruses are limited. Here, we amplified single genomes and characterized viruses, some of which were previously classified as subtype D by sub-genomic pol sequencing that were transmitted in Uganda between December 2006 to June 2011. Analysis of 5′ and 3′ half genome sequences showed 73% (19/26) of infections involved single virus transmissions, whereas 27% (7/26) of infections involved multiple variant transmissions based on predictions of a model of random virus evolution. Subtype analysis of inferred transmitted/founder viruses showed a high transmission rate of inter-subtype recombinants (69%, 20/29) involving mainly A1/D, while pure subtype D variants accounted for one-third of infections (31%, 9/29). Recombination patterns included a predominance of subtype D in the gag/pol region and a highly recombinogenic envelope gene. The signal peptide-C1 region and gp41 transmembrane domain (Tat2/Rev2 flanking region) were hotspots for A1/D recombination events. Analysis of a panel of 14 transmitted/founder molecular clones showed no difference in replication capacity between subtype D viruses (n = 3) and inter-subtype mosaic recombinants (n = 11). However, individuals infected with high replication capacity viruses had a faster CD4 T cell loss. The high transmission rate of unique inter-subtype recombinants is striking and emphasizes the extraordinary challenge for vaccine design and, in particular, for the highly variable and recombinogenic envelope gene, which is targeted by rational designs aimed to elicit broadly neutralizing antibodies.

The ability to efficiently establish a new infection is a critical property for human immunodeficiency virus type 1 (HIV-1). Although the envelope protein of the virus plays an essential role in receptor binding and internalization of the infecting virus, the structural proteins, the polymerase and the assembly of new virions may also play a role in establishing and spreading viral infection in a new host. We examined Ugandan viruses from newly infected patients and focused on the contribution of the Gag-Pol genes to replication capacity. A panel of Gag-Pol sequences generated using single genome amplification from incident HIV-1 infections were cloned into a common HIV-1 NL4.3 pol/env backbone and the influence of Gag-Pol changes on replication capacity was monitored. Using a novel protein domain approach, we then documented diversity in the functional protein domains across the Gag-Pol region and identified differences in the Gag-p6 domain that were frequently associated with higher in vitro replication.

Anti-glutamic acid decarboxylase (GAD) antibodies have been discovered in a variety of neurological syndromes with unique presentations. These syndromes include limbic encephalitis (LE), stiff person syndrome (SPS), opsoclonus-myoclonus-ataxia syndrome, cerebellar ataxia, status epilepticus, and palatal myoclonus among others. We present two patients who presented with Guillain-Barré (GBS) and myasthenia gravis (MG) like syndromes, who were found to have anti-GAD antibodies. These case reports highlight the complex presentation of patients with neurological disorders associated with anti-GAD antibodies. The proper identification of anti-GAD antibody’s presence has proven to be beneficial in treatment and provide enhanced quality of life.

Low-grade appendiceal mucinous neoplasm (LAMN) is a rare malignancy with symptoms varying depending on the clinical manifestations. The most worrisome complication of this particular neoplasm is seeding of mucin into the adjacent peritoneum leading to pseudomyxoma peritonei (PMP). There is a lack of standardized treatment approach; however, an appendectomy-only approach is currently being used for the resection of non-metastatic disease. We present an unusual case of a 67-year-old male found to have LAMN status post elective appendectomy, six months after being treated for an appendiceal abscess.