ABSTRACT
We describe a case of fetal death associated with a recent infection by Chikungunya virus (CHIKV) in a Brazilian pregnant woman (positive RT-PCR in blood and placenta). Zika virus (ZIKV) infection during pregnancy was also identified, based on a positive RT-PCR in a fetal kidney specimen. The maternal infection caused by the ZIKV was asymptomatic and the CHIKV infection had a classical clinical presentation. The fetus had no apparent anomalies, but her weight was between the 3rd and 10th percentile for the gestational age. This is the second case report of congenital arboviral co-infection and the first followed by antepartum fetal death.
Subject(s)
Chikungunya Fever/virology , Fetal Death/etiology , Placenta/virology , Pregnancy Complications, Infectious/virology , Zika Virus Infection/virology , Brazil , Chikungunya Fever/pathology , Coinfection/virology , Female , Gestational Age , Humans , Pregnancy , Pregnancy Complications, Infectious/pathology , Young Adult , Zika Virus Infection/pathologyABSTRACT
OBJECTIVES: Feline immunodeficiency virus (FIV) is a lentivirus that induces AIDS-like disease in cats. Some of the antiretroviral drugs available to treat patients with HIV type 1 are used to treat FIV-infected cats; however, antiretroviral therapy (ART) is not used in cats as a long-term treatment. In this study, the effects of long-term ART were evaluated in domestic cats treated initially with the nucleoside transcriptase reverse inhibitor (NTRI) zidovudine (AZT) over a period ranging from 5-6 years, followed by a regimen of the NTRI lamivudine (3TC) plus AZT over 3 years. METHODS: Viral load, sequencing of pol (reverse transcriptase [RT]) region and CD4:CD8 lymphocyte ratio were evaluated during and after treatment. Untreated cats were evaluated as a control group. RESULTS: CD4:CD8 ratios were lower, and uncharacterized resistance mutations were found in the RT region in the group of treated cats. A slight increase in viral load was observed in some cats after discontinuing treatment. CONCLUSIONS AND RELEVANCE: The data strongly suggest that treated cats were resistant to therapy, and uncharacterized resistance mutations in the RT gene of FIV were selected for by AZT. Few studies have been conducted to evaluate the effect of long-term antiretroviral therapy in cats. To date, resistance mutations have not been described in vivo.
Subject(s)
CD8-Positive T-Lymphocytes , Cat Diseases/drug therapy , Feline Acquired Immunodeficiency Syndrome/drug therapy , Immunodeficiency Virus, Feline/drug effects , Lamivudine/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , Animals , Cats , Follow-Up Studies , Molecular Sequence Data , Viral Load , Zidovudine/therapeutic useABSTRACT
BACKGROUND: Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus that infects cats. The primary mode of transmission occurs through bite wounds, and other routes are difficult to observe in nature. FINDINGS: The purpose of this study was to evaluate FIV transmission from queen to kitten in a colony of naturally infected stray cats. With this aim, a queen was monitored over a period of three years. A blood sample was taken to amplify and sequence gag, pol and env regions of the virus from the queen, two kittens and other cats from the colony. CONCLUSION: Phylogenetic analysis showed evidence of queen to kitten transmission.
Subject(s)
Feline Acquired Immunodeficiency Syndrome/transmission , Immunodeficiency Virus, Feline/physiology , Infectious Disease Transmission, Vertical/veterinary , Animals , Cats , Feline Acquired Immunodeficiency Syndrome/virology , Female , Immunodeficiency Virus, Feline/classification , Immunodeficiency Virus, Feline/genetics , Immunodeficiency Virus, Feline/isolation & purification , Male , Molecular Sequence Data , Pedigree , Phylogeny , Pregnancy , Retroviridae Proteins/geneticsABSTRACT
HIV polymorphism is responsible for the selection of variant viruses resistant to inhibitors used in AIDS treatment. Knowledge of the mechanism of resistance of those viruses is determinant to the development of new inhibitors able to stop, or at least slow down, the disease's progress caused by new mutations. In this paper, the crystallization and preliminary crystallographic structure solution for two multi-resistant 99 amino acid HIV proteases, both isolated from Brazilian patients failing intensive anti-AIDS therapy are presented, viz. the subtype B mutant, with mutations Q7K, S37N, R41K, K45R, I54V, L63P, A71V, V82A and L90M, and the subtype F (wild type), naturally carrying mutations Q7K, I15V, E35D, M36I, S37N, R41K, R57K, D60E, Q61N, I62V, L63S, I64L and L89M, with respect to the B consensus sequence. Both proteins crystallized as a complex with the inhibitor TL-3 in space group P6(1)22. X-ray diffraction data were collected from these crystals to resolutions of 2.1 and 2.6 A for the subtype B mutant and subtype F wild type, respectively, and the enzyme structures were solved by molecular replacement. The crystals of subtype F HIV protease are, to the best of the authors' knowledge, the first protein crystals obtained for a non-B HIV protease.
